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Frontiers in Nanotechnology ·

Volume 8 - 2026 | https://doi.org/10.3389/fnano.2026.1945218

Plant mediated nanoparticles from Cissus quadrangularis L.: a comprehensive review on antimicrobial resistance, biological activities and therapeutic applications

  • K. Vinoth1
  • S. Ramesh Kumar1*corresponding author
  1. VIT School of Agricultural Innovations and Advanced Learning, Vellore Institute of Technology, Vellore, Tamil Nadu, India
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Abstract

Cissus quadrangularis L. (CQ) is one of the most promising medicinal plants owing to its prominent phytochemical composition and pharmacological potentiality. The current review provides an insight into the recent progress of CQ based nanoparticles. The biosynthesis of plant-based nanoparticles using CQ extract was found to be an efficient, cost effective, and eco-friendly approach to conventional chemical methods due to presence of phenolics, flavonoids, and other phytochemicals. In the case of CQ, Silver nanoparticles were extensively used followed by zinc oxide, copper oxide, calcium oxide, titanium dioxide and nanocomposite. The synthesized nanoparticles demonstrated potent antibacterial and antifungal activity against a wide range of bacteria and fungi including multidrug resistant strains as well as antioxidant, anti-inflammatory, anticancer, wound healing, and antidiabetic effects. CQ nanoparticles application in bone, dentistry, tissue engineering, drug targeting, biomaterials, and other fields was also well explored. Most of the studies have been carried out only at the preclinical level. The current review focuses on in depth clinical and toxicological evaluation to explore all possible therapeutic avenues and establish the biosafety and commercial viability of developing new medicines and therapeutics.

Keywords

1 Introduction

Antimicrobial resistance (AMR) is an emerging threat in global public health that is responsible for more than 700,000 annual deaths, which indicates the expected annual deaths up to 10 million by 2050 if the present trend persists (Murugan et al., 2025; Sharma et al., 2025). Apart from public health problems, AMR leading to higher morbidity and mortality worldwide due to resistant pathogens (Murray et al., 2022). It impacts the effectiveness of healthcare operations by limiting the efficacy of surgical operations, cancer therapy, and infection prevention measures (Murugan et al., 2025). The reduced efficacy of conventional antimicrobial therapy may expand the sickness period and also has led to an increase in the use of expensive toxic alternatives (World Health Organization, 2023). Conventional antibiotics are becoming increasingly ineffective due to bacteria’s resistance to them and in case of infections by multidrug resistant organisms, there are hardly any options left to treat infections (Elkelish, 2024). The nanotechnology based approaches to antimicrobial agents describe antimicrobial resistance as the key motivator for creating alternatives that would either target the pathogens directly or increase the efficacy of the antimicrobials. Nanotechnology is being considered is that it allows for better targeting, stabilization, release and increased availability of the antimicrobial drugs (Sharma et al., 2025). As a result, nanomaterials have been viewed as potential substitutes due to multiple modes of action against pathogens, increased efficiency of antimicrobial activity, and reduced possibility of developing resistance (Baptista et al., 2018; Pelgrift and Friedman, 2013). Nanomaterials can be used to improve the potency of antimicrobials and overcome problems related to resistance development. The plant-based antimicrobial substances suffer from translation problems such as low solubility, low stability, reproducibility problems, and lack of bioavailability (Murugan et al., 2025). In addition, green plant mediated synthesis is considered to be eco-friendly and sustainable with less toxic compared to chemically produced nanoparticles (Yellamanda et al., 2025). There is an interest in using medicinal plants in nanotechnology because the phytochemicals found in them act as reducing, capping, and stabilizing agents for nanoparticle preparation (Rajeshkumar et al., 2021; Duraisamy et al., 2024; Nocedo-Mena and Kharissova, 2024).

Cissus quadrangularis L (Family: Vitaceae) is a perennial medicinal plant with a broad distribution in the tropical and subtropical areas of Asia and Africa, which has been widely used in the traditional medical practices like Ayurveda in the treatment of bone fracture, inflammation, digestive ailments, and infections (Mishra et al., 2010). The curative potential of CQ is largely due to its bioactive constituents such as flavonoids, triterpenoids, stilbenes, phytosterols, iridoids, carotenoids, vitamin C, and other phenolic compounds with their antioxidant, antimicrobial, anti-inflammatory, osteogenic, and wound healing actions (Atanasov et al., 2021). Recently, these bioactive compounds have gained popularity in their use as reducing, stabilizing, and capping agents in the synthesis of metal and metal oxide nanoparticles by green synthesis approaches as opposed to the conventional chemical and physical methods (Iravani, 2011; Ahmed et al., 2016). The green-synthesized nanoparticles obtained through CQ have exhibited an improvement in their physicochemical properties and biological activities, such as their strong antibacterial, antifungal, antioxidant, anticancer, anti-inflammatory, larvicidal, photocatalytic, and wound-healing activities, due to the synergistic effects of the bioactive phytoconstituents and nanomaterials (Ahmed et al., 2016). In addition to that, the special features of nanoparticles, such as high surface area to volume ratio, enhanced cellular uptake, controlled drug delivery, and multiple ways of antimicrobial action, make nanomaterials produced by CQ a promising option for overcoming antimicrobial resistance, medical application, environmental restoration, and agriculture (Baptista et al., 2018). Thus, the current review focus on comprehensive analysis of the present state of green synthesis of nanoparticles from CQ, their characterization, biological activities, mechanism of action, and possible applications as well as possible research directions for further application of these nanomaterials in clinical and therapeutic uses.

1.1 Literature search strategy

A systematic literature search was done using databases like PubMed, Scopus and Google Scholar to find literature pertaining to C. quadrangularis, green synthesis nanoparticles, phytochemicals, medicinal uses, and nanomedicine. The search involved the use of combinations of different keywords like “C. quadrangularis,” “CQ,” “Cissus quadrangularis nanoparticles,” “green synthesis,” “nanoparticles,” “phytochemicals,” “therapeutic applications,” and “toxicity” for articles published in the period 2015 to 2026. Original research papers and pertinent reviews on nanoparticle synthesis, characterization, biological activity, medicinal uses, and toxicity were selected. The articles that were duplicate, abstracts from conferences, articles not written in English language, and irrelevant literature to the topic CQ and nanoparticles were excluded.

2 CQ nanoparticle green synthesis

2.1 Green synthesis principles and stages of CQ nanoparticle

Green synthesis through CQ involves the replacement of hazardous chemicals and high energy methods with aqueous extract of plants to operate through a simplified procedure with minimal waste generation (Jadoun et al., 2020; Kasi et al., 2021; Shiraz et al., 2023). In plant mediated nanotechnology, the essential steps include reduction, nucleation, growth/aggregation, and capping with this the quality of the particles is greatly influenced by pH, temperature, reaction time, and concentration of precursors (Khan et al., 2022; Zuhrotun et al., 2023). While plant-based methods are preferred due to the absence of hazardous chemicals and high energy consumption (Hanna et al., 2025) but green synthesis requires standardization of mechanism and kinetics for broader reproducibility (Kumari et al., 2024). The CQ AgNP synthesis process was stated as being simple, economical, and environmentally friendly (Vanaja et al., 2013). Figure 1 explains the green synthesis mechanism of silver nanoparticles (AgNPs) using CQ aqueous extract.

Schematic representation of the green synthesis mechanism of silver nanoparticles (AgNPs) using CQ aqueous extract. Redrawn and adapted from Gayathri et al. (2025).
Figure 1. Schematic representation of the green synthesis mechanism of silver nanoparticles (AgNPs) using CQ aqueous extract. Redrawn and adapted from Gayathri et al. (2025).

2.2 Role of phytochemical in CQ nanoparticle green synthesis

In the CQ system, phytochemicals act as reducing, capping, and stabilizing agents by transforming metal ions into nanoparticles and controlling aggregation (Duraisamy et al., 2024; Pavithra et al., 2025; Shiraz et al., 2023). Phenolic, amine, carboxyl, alkaloid, polyphenolic, terpenoid, tannin, and related biomolecular groups were repeatedly identified by Fourier transform infrared spectroscopy (FTIR) as participants in these processes. The phytochemical composition is a determining factor in nanoparticle size, shape, stability, and activity (Vanaja et al., 2013; Kasi et al., 2021; Kumari et al., 2024). Extracts of CQ contain alkaloid, tannin, phenol, terpenoid, steroid, and saponin (Nandini et al., 2025). Alkaloid, polyphenol, flavonoid, sugar, protein, and terpenoid were identified in general phytochemical tests as major reducing and stabilizing agents (Hanna et al., 2025; Zuhrotun et al., 2023). Phenolate and related groups can donate electrons to metal ions, controlling nanoparticle formation (Rathod et al., 2024).

2.3 Types of nanoparticles synthesized using Cissus quadrangularis

The production of the silver nanoparticles was rapid under optimal conditions, with absorption spectra being detected in the region of 430–450 nm. Additionally, the silver nanoparticles exhibited a crystalline structure and mostly assumed a spherical shape and had sizes ranging from 8.68 nm or 100 nm based on the specific experimental setup and source (Duraisamy et al., 2024; Valli and Vaseeharan, 2012). The gold (Au) and titanium dioxide (TiO2) nanoparticles have wide coverage in pertaining to the plant mediated green synthesis of nanomaterials (Jadoun et al., 2020; Khan et al., 2022). On the contrary, the accessible CQ studies includes the synthesis of different types of nanomaterials such as mesoporous silica (MSN), nanohydroxyapatite (nHAp), tripartite AgNP–MSN–nHAp nanocomposites, and zinc-doped iron oxide (Zn@Fe2O3) nanomaterials (Nandini et al., 2025; Pavithra et al., 2025). In particular, the most extensively studied and well-known type of nanomaterial synthesized from the extract of CQ is the silver nanoparticles (AgNPs), which indicates its significance in the current scientific research field (Kanimozhi et al., 2022). Additionally, zinc oxide (ZnO) and copper oxide (CuO) nanoparticles can be synthesized with CQ extract possessing certain biological activities (Sathappan et al., 2021; Kasi et al., 2021). Figure 2 depicts mechanism of ZnO NPs formation from CQ stem.

Mechanism of ZnO NPs formation from CQ stem. Redrawn and adapted from Gayathri et al. (2025).
Figure 2. Mechanism of ZnO NPs formation from CQ stem. Redrawn and adapted from Gayathri et al. (2025).

The successful fabrication of Fe2O3, Zn@Fe2O3, silica-based nanostructured materials, and hydroxyapatite-based composite nanostructures signifies that the usage of CQ is not limited to the synthesis of single-metal nanoparticles but indicates a wide range of applications in the development of various nanostructures using this versatile green nano biobased system (Pavithra et al., 2025; Nandini et al., 2025). CQ, as a whole, can be considered to be a believable source of green nanotechnology because the extracts from it provide all the reactions required to make nanoparticles. Among the provided evidence, AgNPs, ZnO, CuO, and iron oxide nanoparticles have the highest levels of evidence for CQ, whereas there is no such evidence for AuNPs and TiO2 nanoparticles. Figure 3 explains formation mechanism of Fe3O4 utilizing CQ plant extract.

Formation mechanism of Fe<sub>3</sub>0<sub>4</sub> utilizing CQ plant extract. Redrawn and adapted from Bharathi & Thambidurai, (2024)
Figure 3. Formation mechanism of Fe304 utilizing CQ plant extract. Redrawn and adapted from Bharathi & Thambidurai, (2024)

3 Characterization of CQ derived nanoparticles

3.1 Optical and functional-group analysis

Green synthesis of nanoparticles employing CQ invariably uses multiple analyses for confirming the formation, structure, size, and stability prior to the investigation of their biological effects. UV-Visible spectroscopy helps in proving the formation of nanoparticles through the detection of surface plasmon/band-edge peaks (e.g., for Ag NPs at ∼450 nm; for ZnO NPs at ∼361–378 nm; and for TiO2 NPs at 269 nm) and kinetics of the reaction process (Nandini et al., 2025). FTIR spectroscopy helps to identify the functional groups of the plants that participate in the reduction, capping, and stabilization of the nanoparticles and nanocomposites (Pavithra et al., 2025; Sinthiya et al., 2024). General FTIR reviews emphasize its role in capping and stabilizing groups in green syntheses (Sai et al., 2020).

3.2 Structural and phase characterization

XRD analysis gives information on crystalline phase, purity, crystallite size, and formation of metal/metal oxide phases (Ag, ZnO, CaO, Fe2O3, Zn@Fe2O3, CuO, CaO-containing composites, and nanocellulose crystallinity) (Pasieczna-Patkowska et al., 2025; Bhattacharjee, 2016; Marquis et al., 2016). The aerial part of CQ resulted in the production of almost 24 nm of silver nanoparticles, which were characterized by UV-Vis spectroscopy (SPR peak at 425 nm), FTIR, FESEM, and EDAX analysis. The synthesized nanoparticles showed comparable DPPH free radical scavenging activity and α-amylase inhibitory potential to the standard drug acarbose (Sai et al., 2020). Table 1 depicts the overview of synthesized nanoparticles using CQ extracts.

TABLE 1. Overview of nanoparticles synthesized using Cissus quadrangularis: plant source, synthesis conditions, characterization, and applications.

Nanoparticle typePlant part/ExtractSynthesis conditionsCharacteristicsApplicationsReferences
AgNPsCQ stem aqueous extractMaximum synthesis reported within 1 h, at pH 8, 1 mM AgNO3, 70 °CCrystalline; mostly spherical with some rod/triangular forms; 37–44 nmAntibacterial activity against Klebsiella planticola and Bacillus subtilis(Vanaja et al., 2013)
CQ stem aqueous extractOptimum conditions reported as 15 mL extract, 0.10 mM AgNO3, 20 mL AgNO3, 10 min, pH 11, 45 °CSpherical, highly crystalline; mean diameter 8.68 nm; aggregates 3–20 nm seen by SEMAntibacterial activity against S. aureus and E. coli(Duraisamy et al., 2024)
CQ extractRapid biosynthesis within 20–30 minWell-dispersed, spherical; 50–100 nm; SPR at 450 nmAntibacterial activity at 10 μg/mL MIC against Gram-positive and Gram-negative bacteria with possible aquatic bacteria control(Valli and Vaseeharan, 2012)
CQ leaf aqueous extractGreen synthesis using aqueous leaf extractCrystalline; average crystallite size 35 nm; SPR at 450 nmAntimicrobial activity against Gram-positive and Gram-negative bacteria(Mahendran et al., 2021)
CQ aqueous extractGreen synthesis confirmed by UV-vis, FTIR, FESEM, EDAXStructural confirmationAntioxidant and α-amylase inhibition near acarbose and proposed antidiabetic uses(Sai et al., 2020)
ZnO NPsCQ stem aqueous extractGreen synthesis using stem aqueous extractSpherical; ∼75–90 nm; absorbance at 378 nmAntibacterial activity against M. smegmatis at 50 μg/mL; antiproliferative in MIA PaCa-2 cells, IC50 7.02 ± 0.02 μg/mL at 24 h(Sathappan et al., 2021)
CuO NPsCQ plant extractEco-friendly synthesis using plant extractSpherical; 30 ± 2 nmAntifungal against A. niger and A. flavus; 83%–86% and 81%–85% inhibition at 500–1000 ppm(Devipriya and Roopan, 2017)
CQ leaf extractCopper sulphate precursor; phytochemicals act as reducing agentsOrthorhombic crystallites ∼32.54 nm; irregular spherical morphology; TEM size 50 nmAntibacterial effects(Kasi et al., 2021)
CQ leaf powder/extract1 g plant powder in 100 mL water, boiled 2 min; 20 mL filtrate +80 mL water; 10 mM CuSO4; shaken 24 hCharacterized by XRD, TGA, FTIR, AFM, SEMAntibacterial, antifungal, antioxidant, antidiabetic, anti-inflammatory, and antiproteinase activities(Rajeshkumar et al., 2021)
Ag@Ce NPs/AgNPsCQ plant extractGreen synthesis from CQ extractUV peaks at 370 nm and 350 nm; characterized by XRD, FTIR, SEM-EDAXCd2+ sensing, methylene blue photocatalytic degradation, and antibacterial activity(Pragathiswaran et al., 2021)
CQ-ZnONPs/chitosan nanocompositesCQ -mediated ZnO systemCQ-mediated ZnO synthesis followed by chitosan-conjugated nanocomposite fabricationParticle size 243.3 nm for CQ-ZnONPs and 176.6 nm for CQ-CS/ZnONCs; zeta potentials −15.7 and −16.2 mVAntioxidant, antibacterial, antidiabetic, and wound-healing; wound contraction up to 99.58% ± 0.16%(Gracias et al., 2023)
Ag–nHAp–MSN tripartite nanocompositeCQ aqueous extractTripartite synthesis of silver, mesoporous silica, and hydroxyapatite using aqueous extract as reducing agentPresence and stability confirmed by UV; size and functional groups assessed by XRD and FTIR; DPSC IC50 for composite 131.27 μg/mLBiocompatible with dental pulp stem cells and proposed for dental restorations, coatings, or therapy(Nandini et al., 2025)
Bisphosphonate-conjugated AuNPsCQ stem extractcharacterized by color change, UV, and TEMGold nanoparticle characterization reported, but indexed text does not state particle sizeAntibacterial activity against S. mutans and Lactobacillus; intended for orthodontic anchorage and targeted skeletal delivery(Harikrishnan et al., 2022)
Cellulose nanocrystalsCQ fibersCellulose extraction with gradual lignin removal, then sulfuric acid hydrolysisRod-shaped CNCs; 200–300 nm length, 60–65 nm diameter; crystallinity index 82.39%Reinforcement for sustainable nanocomposites(Sinthiya et al., 2024)
Fe2O3/Zn@Fe2O3CQ stem extractFerric nitrate and zinc nitrate mixed with stem extractCrystalline Fe2O3 and Zn@Fe2O3; Zn doping narrowed bandgapVisible-light methylene blue degradation and environmental remediation potential(Pavithra et al., 2025)

AgNPs: Silver Nanoparticles, ZnO NPs: Zinc Oxide Nanoparticle, CuO NPs: Copper Oxide Nanoparticles, Ag@Ce NPs: Silver–Cerium Nanoparticles ZnONPs: Zinc Oxide Nanoparticles, Ag–nHAp–MSN, tripartite nanocomposite: Silver Nanohydroxyapatite Mesoporous Silica Nanoparticle Tripartite Nanocomposite, Fe2O3: Iron Oxide (Hematite), Fe2O3 NPs: Iron Oxide Nanoparticles, Zn@Fe2O3: zinc doped iron oxide nanoparticles.

4 Biological activities of CQ nanoparticles

The extract of CQ has been utilized extensively as a natural reducing and capping agent for the formation of metallic and metallic oxide nanoparticles. The CQ derived nanoparticles have shown excellent antibacterial, antioxidative, anti-inflammatory, anti-diabetic, osteogenic, and wound-healing properties, largely through in vitro and in vivo studies.

4.1 Antibacterial activity of CQ nanoparticle against diverse bacterial strains

The extraction from CQ has shown direct antibacterial action against Escherichia coli, S. typhi, S. aureus, and Bacillus subtilis under laboratory conditions (Paul, 2024). Methanolic stem extract has also exhibited antibacterial and antifungal properties against various microorganisms using disc diffusion (Payani et al., 2023). The MIC values for both aqueous and ethanolic extracts against Porphyromonas gingivalis were 500 μg/mL and ethanolic extract showed greater antibacterial activity, with a lower IC50 of 194.36 μg/mL compared with 240.46 μg/mL for the aqueous extract (Nair et al., 2024). On the nano particle side, Biosynthesized AgNPs have shown potent antibacterial properties against Gram-positive (Bacillus spp.) and Gram-negative (Pseudomonas and Vibrio spp.) waterborne bacteria. MIC results indicated effective inhibition at 10 μg/mL with total inhibition at 20 μg/mL (Pommerville, 2006). This demonstrates their potential in combating multi-antibiotic-resistant strains.

AgCl-NPs biosynthesized showed excellent antibacterial activity against various strains of both Gram-positive (S. aureus and S. pyogenes) and Gram-negative (E. coli and P. vulgaris) bacteria with MIC values were observed to lie within 3–7 μg/mL, which is far below that of tetracycline (9–12 μg/mL) (Naik et al., 2011; Min et al., 2010). The inhibitory effects were attributed to particle size, bioavailability, and synergistic interactions with AgNPs. Remarkably, the synthesized AgNPs showed higher efficacy than the tested extracts and AgNO3 solution. For instance, against Hippobosca maculata, the LC50 of AgNPs, crude extracts, and AgNO3 solution were 6.30 mg/L, 37.08 mg/L, and 40.35 mg/L, respectively. Similarly, against R. microplus larvae, the LC50 of AgNPs, crude extracts, and AgNO3 solution were 7.61 mg/L, 50.00 mg/L, and 21.72 mg/L, respectively. Notably, 25 mg/L caused 100% mortality of both parasites. Overall, the biosynthesized AgNPs showed enhanced anti-trypanosome activity potential compared to the crude extracts and AgNO3 solution (Santhoshkumar et al., 2012).

A chitosan-coated magnetic nanocomposite was fabricated using CQ extract and characterized by FTIR, XRD, XPS, SEM, and TEM analyses. The obtained nanocomposite demonstrated excellent antibacterial activity against Escherichia coli and S. aureus, antioxidant properties in the DPPH assay, and good antitumor activity against MG-63 osteosarcoma cells with an IC50 value of 54 μg/mL. Moreover, the nanocomposite showed Hemolysis compatibility with human red blood cells (Bharathi and Thambidurai, 2024). Also, stem aqueous extracts resulted in the formation of AgNPs with average size of ∼42.46 nm. The nanoparticles demonstrated strong adulticidal and larvicidal activity against Hippobosca maculata and R. microplus. Moreover, the values of LC50 for tested AgNPs were found to be lower than those of crude extracts and AgNO3, indicating the enhanced antiparasitic activity of synthesized nanoparticles (Santhoshkumar et al., 2012).

4.2 Antioxidant activities CQ nanoparticles

CQ contains flavonoids, triterpenoids, stilbenes, vitamin C, phytosterols, and other phenolic derivatives potentially contributing to the antioxidant and anti-inflammatory activities (Manocchio et al., 2026). In particular, quercetin, daidzein, genistein, resveratrol, piceatannol, β-sitosterol, and related compounds were detected in methanolic extracts of the plant (Manocchio et al., 2026). The extracts showed powerful free-radical scavenging activity, as demonstrated by their strong antioxidant activity both in vitro and in vivo (Sundaran et al., 2020). The high antioxidant activity of methanolic extracts of CQ was mainly attributed to β-carotene (Sundaran et al., 2020). Silver nanoparticles obtained from CQ stem extract consistently showed scavenging activity of DPPH radicals, with the activity in one study having been reported as higher than that of ascorbic acid as a reference compound (Duraisamy et al., 2024). In a comparative analysis, the total alkaloid and phenolic contents were found to be higher in CQ-synthesized silver nanoparticles in comparison to the methanol extract, although the extract demonstrated better antiradical properties (Nazneen, 2024). The phytochemicals, including flavonoids, phenolics, and terpenoids, which were found to be adsorbed onto the surface of the nanoparticles during green synthesis, may act as capping agents responsible for radical scavenging (Rameshwari, 2017; Duraisamy et al., 2024). Zinc oxide and titanium dioxide nanomaterials were also reported as effective antioxidants. The chitosan-coated ZnO nanocomposite (CS-ZnO/CQE) achieved 78.7% ± 0.34% inhibition of DPPH radicals (Bharathi and Thambidurai, 2024). The CQ-ZnO nanoparticles and their chitosan-conjugated counterparts showed free radical scavenging activity in various in vitro assays (Gracias et al., 2023). The CQ-TiO2 nanoparticles were found to effectively scavenge DPPH and ABTS radicals while a CQ-TiO2 scaffold designed for periodontal applications demonstrated good antioxidant activity by exhibiting high inhibition of DPPH radicals (Farjana et al., 2026). Selenium nanoparticles generated from CQ extract (VG-SeNPs) did not inhibit the growth of S. cerevisiae cells, unlike the treatment with the plant extract or sodium selenite, but they were found to regulate superoxide dismutase and catalase activity in favour of cellular antioxidant defence (Chilala et al., 2025). Additionally, no antioxidant activity of CQ nanoparticle samples in vivo was described in the existing studies. The antioxidant activity may also depend on the concentration of the nanoparticles used in a particular formulation, as evidenced by the carrageenan hydrogel scaffold containing 20% w/v of CQ extract showing maximum antioxidant activity, while the activity of a 30% w/v formulation was substantially decreased due to probable particle aggregation (Sairaman et al., 2022).

4.3 Anti-inflammatory activities CQ nanoparticles

Green-synthesized CQ nanoparticles demonstrate anti-inflammatory activity by suppressing pro-inflammatory cytokines and protein denaturation through various metals and metal oxides (Farjana et al., 2026; Rajeshkumar et al., 2021). CQ mediated copper oxide nanoparticles exhibited anti-inflammatory and antiprotease activities, thereby providing a scope for the management of arthritis and other inflammatory conditions (Rajeshkumar et al., 2021). CQ mediated green synthesized silver nanoparticles showed anti-arthritic activity with percent inhibition of 81% and 85% in egg albumin and bovine serum albumin, respectively (Kanimozhi et al., 2022). CQ loaded titanium dioxide nanoparticles caused significant suppression of inflammatory cytokines including IL-6, IL-8, and TNF-alpha in human periodontal ligament cells thus providing rationale for the use of these nanoparticles in the management of periodontitis (Farjana et al., 2026). Green synthesized ZnO nanoparticles from CQ extract showed comparable in vitro anti-inflammatory activity to standard drugs (Arya et al., 2025). However, the anti-inflammatory activity of CQ nanoparticles has not been evaluated in vivo while the crude extract and fractions have shown anti-inflammatory activity in animal models (Kumar et al., 2015; Navarro et al., 2014; Choi et al., 2025). Phytochemical constituents such as flavonoids, phenols, β-sitosterol, and terpenoids present in the CQ mediated nanoparticles might be responsible for the observed anti-inflammatory activity, though this has not been compared to the activity demonstrated by the crude extract (Arya et al., 2025; Farjana and Valiathan, 2025). Thus, there is a need for in vivo investigations to verify the therapeutic potential and safety profile of CQ nanoparticles for the management of inflammatory disorders.

4.4 Wound healing and regenerative potential of CQ nanoparticles

CQ nanoparticle and scaffold-based systems demonstrate convergent regenerative potential for diverse clinical applications due to the combination of CQ’s anti-inflammatory, antioxidant, antimicrobial, and osteoinductive compounds and improved local bioavailability and tissue interactions when delivered by nanostructured nanomaterials such as chitosan/POSS bilayer nanocomposite dressings, scaffolds of poly ethylene glycol gum bioactive hybrids, or PLGA-PEG nanoparticles (Manocchio et al., 2026; Gracias et al., 2023). Specifically, CQ-loaded chitosan/POSS bilayer nanocomposite dressings demonstrated potential for cutaneous wound repair since they enabled the production of nanofibers with a diameter of 77,9–97,4 nm and water-vapor permeability to accelerate healing while maintaining the required level of humidity, delivering up to 78%–80% of the loaded CQ after 4 days of treatment, and improving dermal cell proliferation, wound closure, collagen deposition, and antibacterial properties against Gram-positive and Gram-negative bacteria (Aker et al., 2023). A second CQ-based nanocomposite platform, comprising chitosan-conjugated ZnO nanoparticles biosynthesized from CQ, demonstrated excellent radical-scavenging and antibacterial properties, achieving wound contraction rates of 98.92% and 99.58%, respectively, and promoting chronic tissue repair (Gracias et al., 2023). In periodontal wound models, CQ-containing composite scaffolds were associated with increased closure rates and reduced inflammation in zebrafish, whereas membranes functionalized with CQ carrageenan improved fibroblast migration and upregulated COL1A1, VEGF-A, RUNX2, IL-10, and MMP2 – thus, supporting angiogenesis, osteogenesis, and anti-inflammatory mechanisms (Sitaram et al., 2025; Subramanian et al., 2025). Table 2 explained the antimicrobial, antiparasitic, cytotoxic, and wound-healing activities of CQ mediated nanoparticles and nanocomposites.

TABLE 2. Summary of antimicrobial, antiparasitic, cytotoxic, and wound-healing activities of Cissus quadrangularis-mediated nanoparticles and nanocomposites.

CQ-mediated nanoparticle/formulationTested organism/cellsAssay/parameterReported valueReferences
AgNPsB. subtilisZone of inhibition8, 9, 9, 11, 11 mm at 10, 20, 30, 40, 50 µL(Vanaja et al., 2013)
K. planticolaZone of inhibition9, 10, 9, 12, 13 mm at 10, 20, 30, 40, 50 µL(Vanaja et al., 2013)
Gram-positive/Gram-negative bacteriaMIC10 μg/mL(Valli and Vaseeharan, 2012)
H. maculata adultsLC50/LC906.30/18.14 mg/L(Santhoshkumar et al., 2012)
R. (B.) microplus larvaeLC50/LC907.61/22.68 mg/L(Santhoshkumar et al., 2012)
Hep2 cellsIC5064 μg/mL(Renugadevi et al., 2012)
AgNPsVero cellsIC5090 μg/mL(Renugadevi et al., 2012)
ZnO NPsS. mutans, S. aureus, B. subtilis, E. coli, P. aeruginosaZone of inhibition13–23 mm at 50–150 μL, depending on organism(Khatak et al., 2020)
M. smegmatisEffective antibacterial concentration50 μg/mL(Sathappan et al., 2021)
MIA PaCa-2 cellsIC507.02 ± 0.02 μg/mL at 24 h(Sathappan et al., 2021)
CQ-mediated Ag/n-HAp/MSN compositeDental pulp stem cellsIC50AgNP: 49.004; n-HAp: 106.869; MSN: 113.711; composite: 131.27 μg/mL(Krishnakumar et al., 2025)
CQ-ZnO/chitosan nanocompositeExcision wound modelWound contraction98.92% ± 0.39% (7 mg); 99.58% ± 0.16% (14 mg)(Gracias et al., 2023)

4.5 Bone health and osteogenic potential of CQ nanoparticles

In terms of bone regeneration, functionalization of materials with CQ has consistently demonstrated osteogenic potential; thus, CQ-containing PLLA nanofibers enhanced mesenchymal stem-cell adhesion, proliferation, and osteogenic differentiation independently of osteogenic supplements (Parvathi et al., 2017). Similarly, CQ-loaded chitosan/Na-carboxymethyl cellulose scaffolds ensured adequate pore sizes for bone repair, improved compression modulus (76–654 kPa), and increased osteoblast proliferation, mineralization, and alkaline phosphatase activity (Tamburaci et al., 2018). CQ-biofunctionalized nano-hydroxyapatite ceramic nano-cement also improved bone volume (10.5 ± 2 mm3vs. 6.5 ± 1.2 mm3in the control group) and BV/TV (21% ± 4.2% vs. 13.1% ± 2.5% in the control group) while reducing cellular oxidative stress (Gupta et al., 2023). Moreover, CQ nanoparticles proved beneficial for implant integration since treatment with nanoparticulate CQ extract increased peri-implant bone density, osteoid seam formation, bone formation, and alkaline phosphatase activity and promoted osseointegration in rats (Prabhu et al., 2024). Farjana and Valiathan (2025) and Nandini et al. (2025) reported the early stages of osseointegration were detected within 2 weeks after implant surgery.

4.6 Dental health and scavenging activity of CQ nanoparticles

For dental and periodontal applications, CQ is considered a bioactive regenerative agent since it modulates mesenchymal stem cell fate toward osteoblastogenesis, being loaded into membranes, scaffolds, implant coatings, or restorative nanocomposites. CQ-loaded TiO2 nanoparticles demonstrated antimicrobial impact on periodontal ligament cells in vitro and notable scavenging activity against DPPH radicals, reduced inflammatory cytokines, increased anabolic pathways, and excellent cytocompatibility to become among the most promising dental nanomaterials currently under investigation (Farjana et al., 2026). Other dental nano formulations include CQ-mediated silver–nanohydroxyapatite–mesoporous silica composite, which augmented dental pulp stem-cell proliferation and was suggested as a restorative, coating, or therapeutic material, and gold nanoparticles generated via the CQ-assisted procedure exhibiting antibacterial efficacy against Streptococcus mutans and Lactobacillus with reduced cytotoxicity in the tested assay (Harikrishnan et al., 2022). The clinical relevance of CQ in odontology was further supported by a non-nanoparticle-based study reporting that CQ application enhanced distraction osteogenesis in mandibular alveolar bone, contributing to increased bone density around implants (Altaweel et al., 2021). Notably, the pharmacological efficiency of CQ in various oral tissues also depends on the route of administration since the self-emulsifying system increased the oral bioavailability by approximately 76% (Garg et al., 2024). In relation to the nano scaffolds, 3D printed CQ-alginate/chitosan constructs for cancellous alveolar bone defect repair demonstrated dose-dependent increases in free radical scavenging, cell viability, and mineralization capacity, with the highest performance recorded for the medium CQ dose (Padhihary and Pramanik, 2024). Altogether, the authorized studies provide robust evidence for the therapeutic potential of CQ nanoparticles and nano scaffolds for promoting tissue regeneration with particular emphasis on cutaneous, osseous, and dental applications. However, the majority of the studies based on in vitro and animal experimentation, and the consistent clinical performance necessitates standardized preparations, extensive investigations, and prolonged follow up before entering into the clinical practice (Subramanian et al., 2025).

4.7 Anticancer activity of CQ nanoparticles

CQ medicated ZnO nanoparticles exhibited the most potent anti-proliferative effect with an IC50 value of 7.02 ± 0.02 μg/mL at 24 h in MIA PaCa-2 pancreatic cancer cells (Sathappan et al., 2021). Chitosan-coated CQ-Fe3O4 nanocomposites demonstrated good anti-proliferative activity with IC50 = 54 ± 0.50 μg/mL on MG-63 osteosarcoma cells (Bharathi and Thambidurai, 2024). CQ stem-mediated AgNPs showed moderate anti-proliferative activity with IC50 = 56.74 μg/mL in MCF-7 breast cancer cells; however, their activity was almost 10 times lower than that of cisplatin (IC50 = 5.51 μg/mL) in the same model (Nazneen and Bhavani, 2023). Priyadarshini et al. (2020) reported the silver-based CQ nanomaterials are also effective, but at higher concentrations. CQ-assisted AgNPs exhibited an IC50 = 64 μg for Hep2 cells and 90.3 μg for Vero cells in an initial study. CQ derived nano-silver and silver chloride particles showed anti-proliferative activity against A549 lung cancer cells with IC50 ranging from 85 to 90 μg/mL, whereas normal macrophage cells were more resistant with IC50 equal to 130–140 μg/mL, indicating some selectivity. Nazneen and Bhavani (2023) evaluated the molecular mechanism of anti-proliferative activity, and the results were inconsistent. CQ stem-mediated AgNP treatment resulted in downregulation of p53 tumor suppressor gene by 0.43-fold, although the overall cytotoxic effect was moderate. CQ-ZnO and CQ–Fe3O4 nanocomposites inhibited the growth of cancer cell lines (MIA PaCa-2, MG-63) with acceptable selectivity over normal cells and red blood cells (Sathappan et al., 2021; Kasi et al., 2021).

4.8 Antidiabetic activity of CQ nanoparticles

Molecular docking studies revealed that the phytoconstituents such as kaempferol and quercetin docked efficiently into the active site of α-amylase, which can help in the management of diabetes mellitus (Sai et al., 2020). Zinc oxide nanocomposites conjugated to chitosan showed a significant inhibitory effect on the enzymes α-amylase and α-glucosidase with IC50 of 73.66 ± 1.21 μg/mL and 87.59 ± 1.29 μg/mL, respectively (Gracias et al., 2023). Copper oxide nanoparticles prepared by the CQ method were studied for their antidiabetic activity along with their antimicrobial and anti-inflammatory actions (Rajeshkumar et al., 2021). Molecular docking analysis revealed that the bioactive molecules from CQ, like β-sitosterol, had high binding affinities to diabetes-related proteins (Arya et al., 2025).

5 Mechanisms of antimicrobial action

5.1 Membrane, ROS, and intracellular damage

Membrane damage is the major mechanistic pathway of CQ nanoparticles due to their small size enabling to increase the surface area and adhere to the bacterial membrane (Duraisamy et al., 2024). Overall, more comprehensive information about the mechanism of action of AgNPs demonstrated their ability to penetrate the bacterial wall, disrupt the membrane structure, increase its permeability, and damage transport processes (Fernandes et al., 2023). Duraisamy et al. (2024) reported the production of reactive oxygen species (ROS) as the potential mechanism of action of CQ nanoparticles. Indeed, one of the studies revealed that the high antibacterial activity of CQ-AgNPs was associated with their small size, the presence of bioactive compounds in CQ extract, enhanced production of ROS, and the ability to release silver ions. Additionally, overall mechanism of action of nanoparticles was suggested to be based on the combined effect of physical interactions with the cell membrane and DNA, inhibition of crucial enzymes, and induction of oxidative stress (Fernandes et al., 2023).

5.2 Biofilm, QS, and synergy

Biofilm inhibition and quorum sensing inhibition are related but not directly demonstrated for the case of CQ. The phytochemicals can increase the membrane permeability and reduce its integrity, inhibit DNA and protein synthesis, and interfere with quorum sensing by target signal inhibition and QS gene deregulation (Bouyahya et al., 2022). Quorum sensing is considered as the key process in biofilm formation, EPS production, virulence, and antibiotic resistance. In this regard, natural quorum sensing inhibitors can act synergistically with antibiotics by targeting biofilm and EPS, thus removing the protective barrier and increasing the antibacterial effect (Alum et al., 2025). Notably, the study on the phytochemicals and docking of CQ suggested the synergistic nature of action for campesterol and gamma-sitosterol, with antimicrobial activity being similar to ampicillin in some cases, but it is a separate hypothesis (Paul, 2024). Protein denaturation and DNA damage are not directly demonstrated for CQ. In general, the mechanisms are mostly supported on the level of phytochemicals in medicinal plants and metallic nanoparticles, rather than the direct evidence for CQ antibacterial action (Bouyahya et al., 2022; Fernandes et al., 2023). Thus, the mechanisms with the best suggested evidence for CQ antibacterial action are disruption of membrane integrity and killing of bacteria via ROS-based nanoparticles, while interference with biofilm formation and synergistic antibacterial action with antibiotics can be suggested but require additional evidences.

6 Applications of CQ against antimicrobial resistance

CQ exhibits substantial preclinical efficacy against antimicrobial resistance, with the greatest potential for bacteria, wound healing materials, and local delivery mechanisms. The studies demonstrate CQ antibacterial potential, including treatment options for multidrug-resistant infections, antimicrobial-resistant fungal strains, biofilm-related complications, wound healing materials, coating properties, and antimicrobial delivery arrangements (Awashra and Młynarz, 2023; Prabhu et al., 2024; Domb et al., 2021). The lyophilized extract of CQ displayed potent antibacterial activity against bacterial strains in vitro study (Awashra and Młynarz, 2023). Other studies utilizing either whole plant or stem extracts of CQ also demonstrated antibacterial activity against Escherichia coli, Klebsiella pneumoniae, S. aureus, Bacillus subtilis, and Porphyromonas gingivalis, with some exhibiting low minimum inhibitory concentration and minimum bactericidal concentration against Gram-negative bacteria (Salsabila et al., 2025; Nandini et al., 2025). The antibacterial potential of CQ-derived nanomaterials was also utilized against bacterial strains, with the chitosan-ZnO/CQ composite displaying inhibition zones of 19 ± 1.00 mm against Staphylococcus aureus and 17 ± 1.05 mm against E. coli (Bharathi and Thambidurai, 2024). Similar antibacterial activities were reported for CQ chitosan/ZnO nanocomposites against selected bacterial strains. The antifungal potential of CQ was also reported in vitro but antibacterial activity was more prominent in a comparative analysis (Salsabila et al., 2025).

Specifically, CQ stem extract showed antifungal activity against a panel of fungi by the disc diffusion assay (Khan et al., 2025). Copper oxide nanoparticles synthesized using CQ extract were exploited for antifungal applications, thus providing a concept for combating resistant fungal strains (Bharathi and Thambidurai, 2024). Periodontal infection has relevance to the discussion because poor debridement allows antibiotics to be ineffective through the biofilm barrier, increased MIC, and high resistance of P. gingivalis to common antibiotics. CQ extracts inhibited the growth of P. gingivalis (Salsabila et al., 2025). In general, the property of a continuous release of antimicrobial substances from CQ may be beneficial in a variety of biofilm-associated infections. CQ-loaded bilayer dressings, for instance, released the extract into the medium for 4 days, achieving a cumulative release of 78%–80%. The resulting medium demonstrated antibacterial activity against Gram-positive and Gram-negative bacteria (Prabhu et al., 2024). Similarly, wound healing is regarded as an essential application for CQ-based dressings. Specifically, chitosan/POSS bilayer wound dressings loaded with CQ demonstrated antimicrobial effects while promoting cell proliferation, accelerated wound healing, and enhanced collagen deposition (Prabhu et al., 2024). Another material, namely, CQ-chitosan/ZnO nanocomposites, showed improved healing properties. Thus, the percent of wound contraction achieved 98.92% ± 0.39% and 99.58% ± 0.16% for 7 and 14 mg treatments, respectively, outperforming the standard and CQ-ZnO groups (Prabhu et al., 2024). Bharathi and Thambidurai (2024) and Domb et al. (2021) suggest that CQ will be useful in implant dentistry. Indeed, CQ extract in the form of nanoparticles demonstrated improved osseointegration when applied to implants, while the toxicity profile of the material was evaluated in rats (Prabhu et al., 2024). In another study, a CQ-mediated silver/mesoporous silica/hydroxyapatite composite was shown to exhibit reduced cytotoxicity and increased proliferation of dental pulp stem cells, thus potentially serving as a restorative, coating, or therapeutic material for dental practitioners (Nandini et al., 2025).

The biocompatibility and tissue integration potential of coating is efficient than the direct antibacterial effect against device infections. Moreover, the active ingredient is used to create local drug-delivery-like systems rather than an antimicrobial agent for systemic administration. Safety assessments of nanoparticles highlight the importance of synthesis, functionalization, biodistribution, biological safety, toxicity, and barrier permeability, which are relevant to the CQ nano delivery systems (Pandey et al., 2023). The reviewed studies suggest applying the CQ-based hydrogel dressings and nanocomposite materials for local use due to the prolonged release of the active ingredient and antibacterial effect (Prabhu et al., 2024). The overall safety profile of the studies has also limited the translation of CQ to the clinical setting. Notably, in vitro approaches are insufficient to predict nanoparticle behaviour in vivo and require extensive preclinical trials to assess the kinetics and organ toxicity (Pandey et al., 2023). CQ against antimicrobial resistance agents seems to target multidrug-resistant bacteria, advanced wound healing biomaterials, and local drug-delivery systems, while antifungal resistance proteins, infected biofilm treatment, and coating of medical devices are less proven but promising areas of application. Table 3 depicts the antimicrobial properties of CQ-derived nanoparticles against clinically relevant pathogens and Figure 4 explained the applications of CQ against antimicrobial resistance.

TABLE 3. Summary of antimicrobial properties of Cissus quadrangularis derived nanoparticles against clinically relevant pathogens.

Nanoparticle systemPlant part/ExtractCharacterization/SizePathogens testedAntimicrobial activityMDR/Clinical relevanceOther applicationsReferences
ZnO NPsCQ stem aqueous extractSpherical; ∼75–90 nm; absorbance 378 nmMultiple bacteria, with strongest effect on M. smegmatisEffective inhibition of M. smegmatis at 50 μg/mLAntibacterial potential shown, but MDR status not specifiedAntiproliferative in cancer cells(Sathappan et al., 2021)
CuO NPsCQ plant extractCharacterized by XRD, TGA, FTIR, AFM, SEMAntibacterial and antifungal screeningBiomedical antibacterial potentialRelevant as a plant-mediated antimicrobial platform, but no indexed pathogen-specific MDRAntioxidant, antidiabetic, anti-inflammatory, antiproteinase(Rajeshkumar et al., 2021)
CaO NPsCQ stem aqueous extractCubic and hexagonal; about 58 nmS. aureus, E. coli, K. pneumoniae, P. aeruginosa, S. typhi, S. dysenteriae, V. choleraeMaximum inhibition against E. coli; high MIC activity against all tested organismsIncludes clinically important Gram-negatives such as K. pneumoniae and P. aeruginosaProposed for bactericidal and wound-healing uses(Marquis et al., 2016)
AgCl NPsCQ leaf extractCrystalline; 15–23 nmMDR bacterial strainsAntibacterial activity evaluated by MIC against MDR strainsClearest CQ-specific MDR evidenceSingle-step green synthesis(Gopinath et al., 2013)
AgNPsCQ stem aqueous extractMostly spherical, some rod/triangle; 37–44 nmKlebsiella planticola, Bacillus subtilisGreater antibacterial activity against these species by disc diffusionRelevant because Klebsiella is a clinically important MDR target genus, though this species is not the main hospital pathogen K. pneumoniaeSynthesis depended on pH, temperature, time, and AgNO3 concentration(Vanaja et al., 2013; Dunah et al., 2026)
CQ stem aqueous extractHighly crystalline spherical particles; mean diameter 8.68 nmS. aureus and E. coliSignificant antibacterial activity against both speciesPathogens are major MDR targets in the wider literature, but this study does not itself label them MDRantioxidant activity better than ascorbic acid(Duraisamy et al., 2024)
CQ leaf aqueous extractCrystalline; 35 nm average crystallite; SPR 450 nmGram-positive and Gram-negative bacteriaBactericidal efficacyShows broad-spectrum activity, but indexed text does not specify MDR strainsGreen synthesis via leaf extract(Mahendran et al., 2021)
ZnONPs/ZnONCsCQ-mediated ZnO with chitosan nanocomposite243.3 nm and 176.6 nm; zeta potentials −15.7 and −16.2 mVBacterial pathogensSignificant antibacterial activity for nanoparticles and nanocompositesFormulation can change activity and delivery propertiesWound contraction up to 99.58%(Gracias et al., 2023)

ZnO NPs: Zinc Oxide Nanoparticles, CuO NPs: Copper Oxide Nanoparticles, CaO NPs: Calcium Oxide Nanoparticles, AgCl NPs: Silver Chloride Nanoparticles, AgNPs: Silver Nanoparticles, ZnO NPs: Zinc Oxide Nanoparticles, ZnO NCs: Zinc Oxide Nanocomposites.

Applications of CQ against antimicrobial resistance.
Figure 4. Applications of CQ against antimicrobial resistance.

7 Toxicity, biocompatibility and safety of CQ nanoparticles

7.1 In vitro and cytotoxicity

CQ nanoparticles appear to demonstrate relatively low in vitro toxicity and cytocompatibility, although evidence pertains primarily to preclinical models. Evidence for the in vivo, environmental, and regulatory safety of CQ nanoparticles is limited, with direct evidence regarding the specific safety of CQ nanoparticles being scarce and largely confined to preclinical examinations. CQ-based nanomaterials demonstrated cytocompatibility with normal mammalian cells, but it should be noted that the evidence is limited by the number of tested formulations. The CQ/chitosan-ZnO nanocomposite exhibited reduced toxic effects on human erythrocytes, human dermal fibroblasts, and HEK-293 cells and was biodegradable. CQ/chitosan-Fe3O4 nanocomposite showed improved biocompatibility in human RBCs and L929 fibroblasts (Bharathi and Thambidurai, 2024). Regarding dental pulp stem cells, the CQ-based tripartite composite displayed the highest IC50 among the materials tested, including mesoporous silica (113.711 μg/mL), n-HAp (106.869 μg/mL), and AgNPs (49.004 μg/mL): 131.27 μg/mL. Thus, it was less cytotoxic than AgNPs, and the same study reported that the tripartite composite was least lethal to DPSCs. Moreover, diluted composites promoted cell proliferation, indicating that the material lacks to demonstrate overall biocompatibility but rather biocompatibility in a particular local environment (Nandini et al., 2025).

7.2 In vivo, hemocompatibility, and environment

An implant experiment of nanoparticulate CQ extract was performed, in which biochemical toxicity was analysed prior to and following implantation. The result of bone integration rather than the postulation of negative adverse effects, meaning that evidence of overall safety remains limited (Prabhu et al., 2024). Therefore, CQ’s tolerance might be assumed on a short-term basis. The hemocompatibility of CQ was demonstrated better than its overall in vivo toxicity. Bharathi and Thambidurai (2024) reported on reduced toxicity of CQ/chitosan-ZnO nanocomposites to human erythrocytes and pass the CQ/chitosan-Fe3O4 nanocomposite testing for human red blood cells, suggesting tolerance to the material on an in vitro level. In other chitosan-related nanoparticle studies, hemolysis was reported to be minimal, and tolerance to the material was determined as acceptable, although not specific to CQ (Sonin et al., 2020).

CQ’s safety is mostly discussed in terms of cell viability or tolerance to short-term application, while the general toxicology literature suggests that the toxicity of nanoparticles relates to their size, surface charge, aggregation, dosage, and mode of administration (Ajdary et al., 2018; Sonin et al., 2020; Domb et al., 2021). Thus, the discrepancy between the safety of CQ nanoparticles under study and the factors affecting nanoparticle toxicity may stem from the fact that most of the studies pertain to materials science rather than toxicology research. Evidence of concern was found in the environmental impact assessment of CQ-synthesized silver nanoparticles, which demonstrated increased mortality, DNA fragmentation, tissue erosion, and impaired development in fish and microcrustaceans (Ishwarya et al., 2016).

In general, the toxicity of AgNPs have reported in plants, microorganisms, aquatic organisms and mammalian cells influenced by size of particles, dosage, environmental transformation (Du et al., 2018; Levard et al., 2012). The cytotoxicity of CQ-mediated silver nanoparticles seems to depend on the composition of the nanoparticles, dose, particle properties, and cell model used. According to Krishnakumar et al. (2025), CQ-mediated AgNPs were cytotoxic to dental pulp stem cells with an IC50 value of 49.004 μg/mL. However, the tripartite nanocomposite which contained CQ-mediated AgNPs was cytotoxic with an IC50 value of 131.27 μg/mL; thus, the cytotoxicity of the CQ-mediated AgNPs was higher compared to CQ-mediated AgNP containing tripartite nanocomposite in the same study.

Nonetheless, the results of the experiment is unable to conclude that CQ-mediated AgNPs are generally less cytotoxic than conventionally prepared AgNPs, since there is no direct comparison between both nanoparticles under identical experimental conditions. The CQ-mediated AgNPs have found dose-dependent cytotoxicity of the nanoparticles. Thus, their safety depends on the mode of preparation and biological environment (Ge et al., 2022). Comparative studies with the same particle size, dose, surface properties, exposure time, and cell model are needed to find out whether CQ-mediated synthesis decreases the cytotoxicity of silver nanoparticles. Therefore, clinical application of CQ nanoparticles may entail ecotoxicological risks. Furthermore, the studies on nanoparticle toxicology recommends careful consideration of potential clinical application of similar materials due to the lack of clinical trials for related nanomaterials (Zoe et al., 2023) and mentions the importance of detailed characterization and toxicity assessments before any clinical translation of CQ chitosan nanoparticles in particular (Frigaard et al., 2022). Table 4 explained the toxicity and biocompatibility of CQ nanoparticle.

TABLE 4. CQ nanoparticle toxicity and biocompatibility.

NanomaterialModelSafety/BiocompatibilityMain findingReferences
Ag-MSN-nHAp tripartite compositeDental pulp stem cellsCytotoxicity, proliferationComposite was least lethal; DPSC proliferation increased with diluted composite; IC50 131.27 μg/mL(Nandini et al., 2025)
CQ extract nanoparticles on implantsWistar ratsBiochemical toxicityHigher bone density, osteoid seam, and bone formation(Prabhu et al., 2024)
Bisphosphonate-conjugated AuNPs with CQ extractcytotoxicity modelLethality/cytotoxicity20% lethality at 50 μL concentration(Harikrishnan et al., 2022)
ZnO/chitosan nanocompositeHuman erythrocytes, HDF, HEK-293Hemocompatibility, cytocompatibilityLess toxicity toward erythrocytes, normal cells, and cell migration capacity(Bharathi and Thambidurai, 2024)
Fe3O4/chitosan nanocompositeHuman RBCs, L929 fibroblastsCytotoxicity/biocompatibilityEnhanced biocompatibility was confirmed in RBC and fibroblast testing
carbon quantum dotsCell viability assayCytotoxicity/survivalBiocompatible with minimal cytotoxicity and good survival even at 10.9 mg/mL for up to 4 days(Kansay et al., 2022)
carrageenan hydrogel particles/scaffoldBrine shrimp assayBiocompatibilityBiocompatibility increased dose-dependently as CQ concentration increased(Sairaman et al., 2022)
CuO nanoparticlesBiomedical screening platformToxicity framing onlyNontoxic origin-mediated synthesis, but indexed text does not provide direct cytotoxicity or hemocompatibility values(Rajeshkumar et al., 2021)

8 Challenges of CQ nanoparticles

The central limitations and challenges of CQ nanoparticles include safety concerns, the need for standardized preparations, mechanistic investigations in vivo, environmental variability, and regulatory adaptation. The majority of the reports on the synthesis and short-term efficacy of CQ nanoparticles are in vitro (Shreffler et al., 2019; Ramos et al., 2022; Kus-Liśkiewicz et al., 2021), but dedicated toxicology or clinical translation studies are missing. Some formulations reported for CQ demonstrate considerable potential and were tested in vitro, but the data are limited to specific preparations.

9 Future prospects

The future prospects of CQ nanoparticles are very promising due to their eco-friendly nature, biocompatibility, and diverse biological activities. Their application in antimicrobial therapy is the most promising among the studied areas. The antimicrobial activity of CQ nanoparticles was reported against a wide range of bacteria and fungi, including multidrug-resistant strains, which qualifies them for use in wound healing, antimicrobial coatings, medical devices, and topical creams. Moreover, due to their osteogenic potential, they can be used in combination with nanocomposites for bone regeneration, dental applications, tissue engineering, and local drug delivery. The antioxidant, anti-inflammatory, and enzyme inhibition properties of CQ nanoparticles indicate their potential application in the treatment of diabetes, arthritis, and other inflammatory diseases. Their use in agriculture, cosmetics, biodegradable packaging, bioremediation, tissue engineering, water treatment, and bio composites is also under consideration. Limited data are present regarding the pharmacokinetics, biodistribution, metabolism and excretion of CQ based nanoparticles. Even though a number of studies have shown their promising biological effects, there is not enough research on their absorption, circulation in the body, distribution, metabolism, and excretion. The process by which nanoparticles accumulate in certain organs, retention in the organ, and further excretion has also not been well-characterized. In addition to that, lack of standard in vivo pharmacokinetic, biodistribution, and toxicokinetic studies makes it difficult to get a complete understanding of the biological fate and safety of these nanoparticles.

Simultaneously, only a few applications of CQ nanoparticles were tested in vivo, and their practical implementation requires further research to optimize the conditions of their synthesis pharmacokinetics evaluation, safety profiles and conduct preclinical and clinical trials. The development of methods for their large-scale production and the use of multifunctional nanoplatforms will open new horizons for their use in medicine, agriculture and industry.

10 Conclusion

CQ-mediated nanoparticles offer a promising and sustainable nanotechnology platform that possesses great potential for biomedical and industrial applications. The wide range of phytochemicals present in CQ not only contributes to the green synthesis of nanoparticles but also endows them with multiple biological functions. The most studied property of CQ nanoparticle is their ability to combat various strains of bacteria and fungi, including Gram-positive and Gram-negative bacteria, pathogenic fungi species, and multidrug-resistant pathogens. Moreover, CQ extract and nanoparticles have demonstrated antimicrobial, biocompatible, and regenerative properties for applications in dentistry and periodontics, including the restoration of periodontal tissues. Notably, CQ-NPs showed anti-proliferative effects against several cancer cell lines, suggesting their potential as anti-cancer agents. Altogether, numerous studies have demonstrated that CQ-NPs are versatile and multifunctional nanomaterials that can be used in antimicrobial, regenerative, and dentistry fields, as well as anticancer drug development. Despite the promising therapeutic applications of CQ nanoparticles, several major hurdles still exist in terms of translating such promising therapeutic results from bench to bedside. Pharmacokinetic and biodistribution analysis is necessary since the pharmacokinetics and biodistribution profile of these particles depends greatly on the size, surface charge, structure, coatings, and composition of the nanoparticles, which affects not only their therapeutic effects but also the possibility of toxicological risks associated with them. Manufacturing and scale-up following GMP guidelines is equally important due to the differences in the particle size, surface characteristics, and purity of the particles depending on synthesis conditions. Moreover, there needs to be well-defined qualities of safety and effectiveness, and non-standardized approaches to regulation of different nanoparticles may slow down the process even more. Plant based nanoparticles, variability in plant source, geographical provenance, collection, extraction and synthesis parameters as well as phytochemistry may result in nanoparticles with different physicochemical and biological characteristics. The long-term safety needs to be considered as most of the study has been done with short-term effects while the long-term exposure can result in organ accumulation, immune response, genotoxicity, oxidative stress and even reproductive toxicity. Thus, there is a need for standard preparation and characterization techniques, pharmacokinetics and toxicology studies, GMP manufacturing and clinical testing of CQ nanoparticles.

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Footnotes

Edited by: Iseli L. Nantes, Universidade Federal do ABC, Brazil

Reviewed by: Esraa A. Elhawary, Ain Shams University, Egypt

Rathish Kumar Sivaraman, Sri Ramakrishna College of Arts and Science (SRCAS), India

Statements

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the Vellore Institute of Technology, Vellore, 632014.

Author contributions

KV: Writing – review and editing, Validation, Conceptualization, Formal Analysis, Resources, Writing – original draft, Visualization, Data curation. SK: Supervision, Investigation, Validation, Writing – review and editing, Visualization.

References

  1. Ahmed S., Ahmad M., Swami B. L., Ikram S. (2016). A review on plants extract mediated synthesis of silver nanoparticles for antimicrobial applications: a green expertise. J. Adv. Res. 7 (1), 17 – 28. doi:10.1016/j.jare.2015.02.007
  2. Ajdary M., Moosavi M., Rahmati M., Falahati M., Mahboubi M., Mandegary A. (2018). Health concerns of various nanoparticles: a review of their in vitro and in vivo toxicity. Nanomaterials 8 (9), 634. doi:10.3390/nano8090634
  3. Aker S., Tamburacı S., Tihminlioglu F. (2023). Development of cissus Quadrangularis -loaded POSS-reinforced chitosan-based bilayer sponges for wound healing applications: drug release and in vitro bioactivity. ACS Omega 8, 19674 – 19691. doi:10.1021/acsomega.3c00999
  4. Altaweel A. A., Baiomy A., Shoshan H. S., Abbas H., Abdel-Hafiz A. A., Gaber A. E.-H. (2021). Evaluation of osteogenic potential of Cissus quadrangularis on mandibular alveolar ridge distraction. BMC Oral Health 21, 491. doi:10.1186/s12903-021-01847-y
  5. Alum E., Gulumbe B., Izah S. C., Uti D., Aja P., Igwenyi I. O. (2025). Natural product-based inhibitors of quorum sensing: a novel approach to combat antibiotic resistance. Biochem. Biophysics Rep. 43, 102111. doi:10.1016/j.bbrep.2025.102111
  6. Arya R., Manueel D. D., Judith J., Harishni V. P., Kingsley J. (2025). Green synthesis of ZnO nanoparticles from Cissus quadrangularis for anti-diabetic and anti-inflammatory applications: a phytochemical and in silico approach. Med. Plants - Int. J. Phytomedicines Relat. Industries 17, 535 – 545. doi:10.5958/0975-6892.2025.00055.4
  7. Atanasov A. G., Zotchev S. B., Dirsch V. M., Banach M., Rollinger J. M. (2021). Natural products in drug discovery: advances and opportunities. Nat. Rev. Drug Discov. 20 (3), 200 – 216. doi:10.1038/s41573-020-00114-z
  8. Awashra M., Młynarz P. (2023). The toxicity of nanoparticles and their interaction with cells: an in vitro metabolomic perspective. Nanoscale Adv. 5, 2674 – 2723. doi:10.1039/d2na00534d
  9. Baptista P. V., McCusker M. P., Carvalho A., Ferreira D. A., Mohan N. M., Martins M. (2018). Nano-strategies to fight multidrug resistant bacteria: a battle of the titans. Front. Microbiol. 9, 1441. doi:10.3389/fmicb.2018.01441
  10. Bharathi V., Thambidurai S. (2024). Phytofabrication of biocompatible chitosan-based ZnO nanocomposite aided by Cissus quadrangularis extract enriched with antimicrobial and antioxidant potential. Int. Journal Biological Macromolecules 271 (Pt 2), 132677. doi:10.1016/j.ijbiomac.2024.132677
  11. Bhattacharjee S. (2016). DLS and zeta potential - what they are and what they are not? J. Controlled Release Official Journal Control. Release Soc. 235, 337 – 351. doi:10.1016/j.jconrel.2016.06.017
  12. Bouyahya A., Chamkhi I., Balahbib A., Rebezov M., Shariati M., Wilairatana P. (2022). Mechanisms, anti-quorum-sensing actions, and clinical trials of medicinal plant bioactive compounds against bacteria: a comprehensive review. Molecules 27, 1484. doi:10.3390/molecules27051484
  13. Chilala P., Jurickova M., Pokorná Z., Motlová T., Horký P., Skalickova S. (2025). Antioxidant properties and antimicrobial activity of selenium nanoparticles synthetized via Zambian medicinal herbs. PLOS One 20, e0325460. doi:10.1371/journal.pone.0325460
  14. Choi Y., Jung J., Bae J., Lee J. K., Kim E. J. (2025). Evaluation of the anti-osteoarthritic effects and mechanisms of Cissus quadrangularis extract containing quercetin and isorhamnetin in a rat model of monosodium iodoacetate-induced osteoarthritis. Food Nutr. Res. 69, 10-29219. doi:10.29219/fnr.v69.12173
  15. Devipriya D., Roopan S. (2017). Cissus quadrangularis mediated ecofriendly synthesis of copper oxide nanoparticles and its antifungal studies against Aspergillus Niger, Aspergillus flavus. Mater. Science and Engineering. C, Mater. Biological Applications 80, 38 – 44. doi:10.1016/j.msec.2017.05.130
  16. Domb A., Sharifzadeh G., Nahum V., Hosseinkhani H. (2021). Safety evaluation of nanotechnology products. Pharmaceutics 13, 1615. doi:10.3390/pharmaceutics13101615
  17. Du J., Tang J., Xu S., Ge J., Dong Y., Li H. (2018). A review on silver nanoparticles-induced ecotoxicity and the underlying toxicity mechanisms. Regul. Toxicol. Pharmacol. 98, 231 – 239. doi:10.1016/j.yrtph.2018.08.003
  18. Dunah M. B., Abdalla M., Wawata I. G., Adekilekun T. N. (2026). Antibacterial activity of plant-extract mediated silver nanoparticles against klebsiella Spp. in Africa: a systematic review. Front. Microbiol. 16, 1673235. doi:10.3389/fmicb.2025.1673235
  19. Duraisamy R., Arizo A., Yilma B. (2024). Antibacterial and antioxidant activity of plant-mediated green synthesized silver nanoparticles using Cissus quadrangularis aqueous extract. Bull. Chem. Soc. Ethiop. 39 (3), 483 – 502. doi:10.4314/bcse.v39i3.8
  20. Elkelish A. (2024). New plant extracts toward multidrug resistance: the convergence of nanotechnology and nanoscience. Spectr. Sci. J. 1 (1), 1 – 14. doi:10.21608/sasj.2024.396119
  21. Farjana H. N., Valiathan G. M. (2025). Cissus Quadrangularis: a comprehensive review as an emerging biomaterial for periodontal regeneration. J. Oral Res. Rev. 17 (1), 87 – 92. doi:10.4103/jorr.jorr_27_24
  22. Farjana H., Valiathan G. M., Jayaraman B. (2026). Green synthesis of cissus quadrangularis -loaded titanium dioxide nanoparticles (CQ-TiO 2) and evaluation of its antimicrobial, antioxidant, anti-inflammatory, and biocompatibility activity in human periodontal ligament cells. Indian Journal Dental Research Official Publication Indian Soc. Dent. Res. 10-4103. doi:10.4103/ijdr.ijdr_724_25
  23. Fernandes M., González-Ballesteros N., Da Costa A., Machado R., Gomes A. C., Rodríguez-Argüelles M. C. (2023). Antimicrobial and anti-biofilm activity of silver nanoparticles biosynthesized with Cystoseira algae extracts. JBIC J. Biol. Inorg. Chem. 28 (4), 439 – 450. doi:10.1007/s00775-023-01999-y
  24. Frigaard J., Jensen J. L., Galtung H., Hiorth M. (2022). The potential of chitosan in nanomedicine: an overview of the cytotoxicity of chitosan based nanoparticles. Front. Pharmacol. 13, 880377. doi:10.3389/fphar.2022.880377
  25. Garg J., Ghoshal G., Sharma G., Katare O., Bhadada S. (2024). Self emulsifying delivery system of cissus Quadrangularis: evidence of enhanced efficacy and promising pharmacokinetic profile in the management of osteoporosis. AAPS PharmSciTech 25, 107. doi:10.1208/s12249-024-02821-x
  26. Gayathri S., Christy A. J., Sagadevan S. (2025). Enhanced antibacterial and anticancer performance of Cissus quadrangularis extract - mediated ZnO nanoparticles via green hydrothermal process. Inorg. Chem. Commun. 179, 114826. doi:10.1016/j.inoche.2025.114826
  27. Ge C., Wang P., Ji D., Xu Z. (2022). Green synthesized silver nanoparticle via Cissus quadrangularis as a Theranostic agent for Colon cancer. Int. J. Pharmacol. 18, 1047 – 1057. doi:10.3923/ijp.2022.1047.1057
  28. Gopinath V., Priyadarshini S., Priyadharsshini N. M., Pandian K., Velusamy P. (2013). Biogenic synthesis of antibacterial silver chloride nanoparticles using leaf extracts of Cissus quadrangularis linn. Mater. Lett. 91, 224 – 227. doi:10.1016/j.matlet.2012.09.102
  29. Gracias S., Ayyanar M., Peramaiyan G., Kalaskar M. G., Redasani V., Gurav N. S. (2023). Fabrication of chitosan nanocomposites loaded with biosynthetic metallic nanoparticles and their therapeutic investigation. Environ. Research 234, 116609. doi:10.1016/j.envres.2023.116609
  30. Gupta A., Mehta S. K., Qayoom I., Gupta S., Singh S., Kumar A. (2023). Biofunctionalization with Cissus quadrangularis phytobioactives accentuates nano-hydroxyapatite based ceramic nano-cement for neo-bone formation in critical sized bone defect. Int. Journal Pharmaceutics 642, 123110. doi:10.1016/j.ijpharm.2023.123110
  31. Hanna D. H., Nady D. S., Wasef M. W., Fakhry M. H., Mohamed F. S., Isaac D. M. (2025). Plant-derived nanoparticles: green synthesis, factors, and bioactivities. Next Mater. 9, 101275. doi:10.1016/j.nxmate.2025.101275
  32. Harikrishnan S., Navaneethan R., Rajesh K. S. (2022). Green synthesis and characterization of bisphosphonate conjugated gold nanoparticle with Cissus quadrangulari s extract to enhance orthodontic Anchorage. Int. J. Health Sci. 6 (S5), 7388 – 7398. doi:10.53730/ijhs.v6ns5.11622
  33. Iravani S. (2011). Green synthesis of metal nanoparticles using plants. Green Chem. 13 (10), 2638 – 2650. doi:10.1039/C1GC15386B
  34. Ishwarya R., Vaseeharan B., Shanthi S., Ramesh S., Manogari P., Dhanalakshmi K. (2016). Green synthesized silver nanoparticles: toxicity against Poecilia reticulata fishes and Ceriodaphnia cornuta crustaceans. J. Clust. Sci. 28, 519 – 527. doi:10.1007/s10876-016-1126-4
  35. Jadoun S., Arif R., Jangid N. K., Meena R. (2020). Green synthesis of nanoparticles using plant extracts: a review. Environ. Chem. Lett. 19, 355 – 374. doi:10.1007/s10311-020-01074-x
  36. Kanimozhi S., Durga R., Sabithasree M., Kumar A. V., Sofiavizhimalar A., Kadam A. A. (2022). Biogenic synthesis of silver nanoparticle using Cissus quadrangularis extract and its invitro study. J. King Saud Univ. - Sci. 34 (4), 101930. doi:10.1016/j.jksus.2022.101930
  37. Kansay V., Sharma V. D., Chandan G., Sharma I., Chakrabarti S., Bera M. (2022). Sustainable synthesis of nitrogen-doped fluorescent carbon quantum dots derived from Cissus quadrangularis for biomarker applications. Mater. Chem. Phys. 296, 127237. doi:10.1016/j.matchemphys.2022.127237
  38. Kasi S. D., Ramasamy J. M., Nagaraj D., Santiyagu V., Ponraj J. S. (2021). Biogenic synthesis of copper oxide nanoparticles using leaf extracts of Cissus quadrangularis and Piper betle and its antibacterial effects. Micro and Nano Lett. 16 (8), 419 – 424. doi:10.1049/mna2.12066
  39. Khan F., Shariq M., Asif M., Siddiqui M. A., Malan P., Ahmad F. (2022). Green nanotechnology: plant-mediated nanoparticle synthesis and application. Nanomaterials 12 (4), 673. doi:10.3390/nano12040673
  40. Khan I. A., Yu T., Yang M., Liu J., Chen Z. (2025). A systematic review of toxicity, biodistribution, and biosafety in up conversion nanomaterials: critical insights into toxicity mitigation strategies and future directions for safe applications. BME Front. 6, 0120. doi:10.34133/bmef.0120
  41. Khatak S., Wadhwa N., Jain P. (2020). Monometallic zinc and bimetallic Cu-Zn nanoparticles synthesis using stem extracts of Cissus quadrangularis (haddjod) and proneness as alternative antimicrobial agents. Biosci. Biotechnol. Res. Asia 17 (4), 763 – 774. doi:10.13005/bbra/2881
  42. Krishnakumar S., Nandini V. V., Thirunavukarasu K., Chinnathambi U., Venkatesh K. V. (2025). Cissus quadrangularis mediated biogenic synthesis of silver-nanohydroxyapatite-mesoporous silica nanocomposite, characterization, and cytotoxicity evaluation dental pulp stem cells. Discov. Nano 20, 150. doi:10.1186/s11671-02-04336-1
  43. Kumar R., Gupta Y., Singh S., Arunraja S. (2015). Cissus quadrangularis attenuates the adjuvant induced arthritis by Down regulating pro-inflammatory cytokine and inhibiting angiogenesis. J. Ethnopharmacology 175, 346 – 355. doi:10.1016/j.jep.2015.08.058
  44. Kumari M., Sadhu P., Talele C., Shah N. (2024). Green nanotechnology: how plants can help synthesize nanoparticles for biomedical and environmental purposes. J. Nat. Remedies 24, 1021 – 1034. doi:10.18311/jnr/2024/36086
  45. Kus-Liśkiewicz M., Fickers P., Tahar B. I. (2021). Biocompatibility and cytotoxicity of gold nanoparticles: recent advances in methodologies and regulations. Int. J. Mol. Sci. 22, 10952. doi:10.3390/ijms222010952
  46. Levard C., Hotze E. M., Lowry G. V., Brown G. E. (2012). Environmental transformations of silver nanoparticles: impact on stability and toxicity. Environ. Sci. and Technol. 46, 6900 – 6914. doi:10.1021/es2037405
  47. Mahendran N., Anand B., Rajarajan M., Muthuvel A., Mohana V. (2021). Green synthesis, characterization and antimicrobial activities of silver nanoparticles using cissus Quadarangularis leaf extract. Mater. Today Proc. 49, 2620 – 2623. doi:10.1016/j.matpr.2021.08.043
  48. Manocchio N., Sorbino A., Devito A., Gallelli L., Romanello D., Rotunno S. (2026). Exploring the role of Cissus quadrangularis in osteoporosis management. Orthop. Res. Rev. 18, 1 – 14. doi:10.2147/orr.s609378
  49. Marquis G., Ramasamy B., Banwarilal S., Munusamy A. P. (2016). Evaluation of antibacterial activity of plant mediated CaO nanoparticles using Cissus quadrangularis extract. J. Photochemistry Photobiology. B, Biol. 155, 28 – 33. doi:10.1016/j.jphotobiol.2015.12.013
  50. Min S. H., Yang J. H., Kim J. Y., Kwon Y. U. (2010). Development of white antibacterial pigment based on silver chloride nanoparticles and mesoporous silica and its polymer composite. Microporous Mesoporous Mater. 128 (1-3), 19 – 25. doi:10.1016/j.micromeso.2009.07.020
  51. Mishra G., Srivastava S., Nagori B. P. (2010). Pharmacological and therapeutic activity of Cissus Quadrangularis: an overview. Int. J. PharmTech Res. 2 (2), 1298 – 1310.
  52. Murray C. J. L., Ikuta K. S., Sharara F., Swetschinski L., Robles Aguilar G., Gray A. (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399 (10325), 629 – 655. doi:10.1016/S0140-6736(21)02724-0
  53. Murugan S., Senthilvelan T., Govindasamy M., Thangavel K. (2025). A comprehensive review on exploring the potential of phytochemicals and biogenic nanoparticles for the treatment of antimicrobial-resistant pathogenic bacteria. Curr. Microbiol. 82 (2), 90. doi:10.1007/s00284-025-04064-w
  54. Naik B., Desai V., Kowshik M., Prasad V. S., Fernando G. F., Ghosh N. N. (2011). Synthesis of Ag/AgCl–mesoporous silica nanocomposites using a simple aqueous solution-based chemical method and a study of their antibacterial activity on E. coli. Particuology 9 (3), 243 – 247. doi:10.1016/j.partic.2010.12.001
  55. Nair A. R., Rajula P. B., Pl R., Geddam S., B S., S L. (2024). Antibacterial activity of Cissus quadrangularis (veldt grape) against Porphyromonas gingivalis, a keystone pathogen in periodontal disease: an in vitro study. Cureus 16 (8). doi:10.7759/cureus.66377
  56. Nandini V., Krishnakumar S., Thirunavukarasu K., Chinnathambi U., Venkatesh K., Nano D. (2025). Cissus quadrangularis mediated biogenic synthesis of silver-nanohydroxyapatite-mesoporous silica nanocomposite, characterization, and cytotoxicity evaluation on dental pulp stem cells. Discov. Nano 20, 150. doi:10.1186/s11671-025-04336-1
  57. Navarro J., Espinosa M. J., Das K., Faraji B., Innis-Whitehouse W., Wei S.-G. (2014). Cissus quadrangularis has anti-oxidant and anti-inflammatory properties: in vitro and in vivo studies (922.15). FASEB J. 28, 922.15. doi:10.1096/fasebj.28.1_supplement.922.15
  58. Nazneen S. (2024). Invitro antioxidant and antidiabetic assay of methanol stem extract and synthesized silver nanoparticles of Cissus quadrangularis L. stem. Acta Bot. Plantae 3, 16 – 22. doi:10.51470/abp.2024.03.02.16
  59. Nazneen s., Bhavani n. l. (2023). Assessment of anticancer activity and gene expression in p53 gene of cissus Quadrangularis. Stem mediated silver nanoparticles. Plant Arch. 23 (Suppl. iment-1), 425 – 429. doi:10.51470/plantarchives.2023.v23.no1.069
  60. Nocedo-Mena D., Kharissova O. V. (2024). Nanoparticles derived from the cissus genus and their antibacterial potential. Environ. Nanotechnol. Monit. and Manag. 22, 100967. doi:10.1016/j.enmm.2024.100967
  61. Padhihary S., Pramanik K. (2024). Development of a novel Cissus quadrangularis extract loaded sodium alginate/chitosan-based 3D printed scaffold for regeneration of cancellous alveolar bone. J. Drug Deliv. Sci. Technol. 104, 106440. doi:10.1016/j.jddst.2024.106440
  62. Pandey R., Vidić J., Mukherjee R., Chang C.-M. (2023). Experimental methods for the biological evaluation of nanoparticle-based drug delivery risks. Pharmaceutics 15, 612. doi:10.3390/pharmaceutics15020612
  63. Parvathi K., Krishnan A. G., Anitha A., Jayakumar R., Nair M. (2017). Poly (L-lactic acid) nanofibers containing Cissus quadrangularis induced osteogenic differentiation in vitro. Int. Journal Biological Macromolecules 110, 514 – 521. doi:10.1016/j.ijbiomac.2017.11.094
  64. Pasieczna-Patkowska S., Cichy M., Flieger J. (2025). Application of fourier transform infrared (FTIR) spectroscopy in characterization of green synthesized nanoparticles. Molecules 30, 684. doi:10.3390/molecules30030684
  65. Paul S. (2024). Antimicrobial activity, phytochemical screening by HPTLC, FTIR and GC-MS of the extracts of Cissus quadrangularis (L.). Afr. J. Biomed. Res. (27), 1203 – 1220. doi:10.53555/ajbr.v27i1s.1212
  66. Pavithra T., Althaf A. M., Ganesh L., Kamalam M. B. R., Roshlin D. R., Inbanathan S. S. R. (2025). Synthesis of zinc–doped iron oxide nanomaterials using cissus Quadrangularis: characterizations and photocatalytic applications. SciEngg Adv. 02 (01), 35 – 43. doi:10.69626/sea.2025.0035
  67. Payani S., Bhaskar M., Kumar G. S., Pradeepkiran J. A. (2023). A study on antimicrobial and anticancer properties of cissus Quadrangulris using lung cancer cell line. Cancer Treatment Research Communications 36, 100732. doi:10.1016/j.ctarc.2023.100732
  68. Pelgrift R. Y., Friedman A. J. (2013). Nanotechnology as a therapeutic tool to combat microbial resistance. Adv. Drug Deliv. Rev. 65 (13–14), 1803 – 1815. doi:10.1016/j.addr.2013.07.011
  69. Pommerville J. C. (2006). Fundamentals of Microbiology. Sudbury, MA, United States: Jones and Bartlett Publishers.
  70. Prabhu S. S., Aparna I., Mutalik S., Khan S., Kamath S., Radhakrishnan R. (2024). Osteoinductive effect of the nanoparticulate form of Cissus quadrangularis ethanolic extract on implant surface in experimental animals. Beni-Suef Univ. J. Basic Appl. Sci. 13, 34. doi:10.1186/s43088-024-00463-3
  71. Pragathiswaran C., Violetmary J., Faritha A., Selvarani K., Nawas P. M. (2021). Photocatalytic degradation, sensing of Cd2+ using silver nanoparticles synthesised from plant extract of Cissus quadrangularis and their microbial activity. Mater. Today Proc. 45, 3348 – 3356. doi:10.1016/j.matpr.2020.12.656
  72. Priyadarshini S., Sonsudin F., Mainal A., Yahya R., Gopinath V., Vadivelu J. (2020). Phytosynthesis of biohybrid nano-silver anchors enhanced size dependent photocatalytic, antibacterial, anticancer properties and cytocompatibility. Process Biochem. 101, 59 – 71. doi:10.1016/j.procbio.2020.11.008
  73. Rajeshkumar S., Menon S., S V., Ponnanikajamideen M., Ali D., Arunachalam K. (2021). Anti-inflammatory and antimicrobial potential of cissus Quadrangularis -assisted copper oxide nanoparticles. J. Nanomater. 2021, 1 – 11. doi:10.1155/2021/5742981
  74. Rameshwari S. (2017). Antimicrobial activities of silver nanoparticles synthesized from Cissus quadrangularis plant extract. Int. J. Approx. Reason. 5, 1171 – 1177. doi:10.21474/ijar01/3930
  75. Ramos T., Villacis-Aguirre C. A., López-Aguilar K. V., Padilla L. S., Altamirano C., Toledo J. R. (2022). The hitchhiker’s guide to human therapeutic nanoparticle development. Pharmaceutics 14, 247. doi:10.3390/pharmaceutics14020247
  76. Rathod S. R., Preetam S., Pandey C., Bera S. P. (2024). Exploring synthesis and applications of green nanoparticles and the role of nanotechnology in wastewater treatment. Biotechnol. Rep. 41, e00830. doi:10.1016/j.btre.2024.e00830
  77. Renugadevi K., Inbakandan D., Muthiah B. (2012). Cissus quadrangularis assisted biosynthesis of silver nanoparticles with antimicrobial and anticancer potentials. Int. J. Pharma Bio Sci. 3 (3), 437 – 445.
  78. Sai N. S., Ranjani S., Hemalatha S. (2020). Synthesis and application of silver nanoparticles using Cissus quadrangularis. Inorg. Nano-Metal Chem. 52, 82 – 89. doi:10.1080/24701556.2020.1862219
  79. Sairaman S., Nivedhitha M., Shrivastava D., Onazi M. A. A., Algarni H., Mustafa M. (2022). Biocompatibility and antioxidant activity of a novel carrageenan based injectable hydrogel scaffold incorporated with cissus Quadrangularis: an in vitro study. BMC Oral Health 22, 377. doi:10.1186/s12903-022-02409-6
  80. Salsabila S., Khairinisa M., Wathoni N., Sufiawati I., Fuad W. E. M., Ikram N. K. K. (2025). In vivo toxicity of chitosan-based nanoparticles: a systematic review. Artif. Cells, Nanomedicine, Biotechnol. 53, 1 – 15. doi:10.1080/21691401.2025.2462328
  81. Santhoshkumar T., Rahuman A. A., Bagavan A., Marimuthu S., Jayaseelan C., Kirthi A. V. (2012). Evaluation of stem aqueous extract and synthesized silver nanoparticles using Cissus quadrangularis against Hippobosca maculata and rhipicephalus (boophilus) microplus. Exp. Parasitol. 132 (2), 156 – 165. doi:10.1016/j.exppara.2012.06.009
  82. Sathappan S., Kirubakaran N., Gunasekaran D., Gupta P., Verma R., Sundaram J. (2021). Green synthesis of zinc oxide nanoparticles (znO NPs) using cissus Quadrangularis: characterization, antimicrobial and anticancer studies. Proc. Natl. Acad. Sci. India Sect. B Biol. Sci. 91, 289 – 296. doi:10.1007/s40011-020-01215-w
  83. Sharma D., Gautam S., Singh S., Srivastava N., Khan A., Bisht D. (2025). Unveiling the nanoworld of antimicrobial resistance: integrating nature and nanotechnology. Front. Microbiol. 15, 1391345. doi:10.3389/fmicb.2024.1391345
  84. Shiraz M., Imtiaz H., Azam A., Hayat S. (2023). Phytogenic nanoparticles: synthesis, characterization, and their roles in physiology and biochemistry of plants. BioMetals 37, 23 – 70. doi:10.1007/s10534-023-00542-5
  85. Shreffler J., Pullan J., Dailey K. M., Mallik S., Brooks A. (2019). Overcoming hurdles in nanoparticle clinical translation: the influence of experimental design and surface modification. Int. J. Mol. Sci. 20 (23), 6056. doi:10.3390/ijms20236056
  86. Sinthiya P., Johnson I., Prabu H., Sahayaraj A. F., Selvan M. (2024). Extraction of cellulose nanocrystals from Cissus quadrangularis for sustainable biocomposite production. Biomass Convers. Biorefinery 15, 10489 – 10501. doi:10.1007/s13399-024-05820-x
  87. Sitaram S., Ganesh B., Kaarthikeyan G., Martin T., Kumar S. (2025). Wound healing evaluation of novel Cissus quadrangularis, bioceramics andtendon extracellular matrix incorporated scaffolds for periodontal boneregeneration with zebrafish models. Bull. Stomatology Maxillofacial Surgery 15 (3), 563 – 569. doi:10.58240/1829006x-2025.3-206
  88. Sonin D., Pochkaeva E., Zhuravskii S., Postnov V., Korolev D., Vasina L. (2020). Biological safety and biodistribution of chitosan nanoparticles. Nanomaterials 10 (4), 810. doi:10.3390/nano10040810
  89. Subramanian B., L M., Martin T., Kaarthikeyan G., Kumar S. (2025). Cissus quadrangularis infused carrageenan membranes: a natural polymer scaffold for periodontal tissue regeneration. Bull. Stomatology Maxillofacial Surgery 21 (7), 188 – 197. doi:10.58240/1829006x-2025.21.7-188
  90. Sundaran J., Begum R., Vasanthi M., Kamalapathy M., Bupesh G., Sahoo U. (2020). A short review on pharmacological activity of Cissus quadrangularis. Bioinformation 16, 579 – 585. doi:10.6026/97320630016579
  91. Tamburaci S., Kimna C., Tihminlioglu F. (2018). Novel phytochemical Cissus quadrangular is extract–loaded Chitosan/na-Carboxymethyl cellulose–based scaffolds for bone regeneration. J. Bioact. Compatible Polym. 33, 629 – 646. doi:10.1177/0883911518793913
  92. Valli J., Vaseeharan B. (2012). Biosynthesis of silver nanoparticles by Cissus quadrangularis extracts. Mater. Lett. 82, 171 – 173. doi:10.1016/j.matlet.2012.05.040
  93. Vanaja M., Gnanajobitha G., Paulkumar K., Rajeshkumar S., Malarkodi C., Annadurai G. (2013). Phytosynthesis of silver nanoparticles by cissus Quadrangularis: influence of physicochemical factors. J. Nanostructure Chem. 3, 1 – 8. doi:10.1186/2193-8865-3-17
  94. World Health Organization (2023). Antimicrobial Resistance. Geneva: World Health Organization. Available online at: (Accessed July 21, 2026).
  95. Yellamanda B., Dasari A. K., Srinivasulu G., Kumar B. L. (2025). Plant-mediated nanoparticles in antimicrobial therapy: a review on cissus quadrangularis -derived CuNPs and AgNPs. Int. J. Adv. Res. 13 (6), 689 – 702. doi:10.21474/IJAR01/21128
  96. Zoe L. H., David S., Rajabalaya R. (2023). Chitosan nanoparticle toxicity: a comprehensive literature review of in vivo and in vitro assessments for medical applications. Toxicol. Rep. 11, 83 – 106. doi:10.1016/j.toxrep.2023.06.012
  97. Zuhrotun A., Oktaviani D. J., Hasanah A. (2023). Biosynthesis of gold and silver nanoparticles using phytochemical compounds. Molecules 28, 3240. doi:10.3390/molecules28073240

Citation

Vinoth, K. & Kumar, S. R. (2026). Plant mediated nanoparticles from Cissus quadrangularis L.: a comprehensive review on antimicrobial resistance, biological activities and therapeutic applications. Frontiers in Nanotechnology, Volume 8. https://doi.org/
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Copyright © 2026 Vinoth and Kumar.

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*Correspondence: S. Ramesh Kumar

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