Distribution of nanotechnology in the cancer therapeutics market as a multimodal treatment: comparison with predecessors and emergence in the commercial field

1 Introduction

Cancer is the second-largest cause of death globally and accounts for approximately 10 million deaths annually, with an estimated 30 million new cases as of 2025 (Siegel et al., 2025). This increasing burden is largely attributed to the complex nature of the cancer, including tumor heterogeneity, metastasis, drug resistance, and adaptive escape mechanisms (Labrie et al., 2022; Roszkowska, 2024; Alshahrani et al., 2025). Conventional treatment modalities, such as surgery, chemotherapy, radiotherapy, and immunotherapy, are often limited by low specificity, systemic toxicity, resistance development, and inadequate therapeutic control (Zafar et al., 2025). For instance, standard chemotherapy involving drugs such as doxorubicin was observed to cause toxicity by killing both malignant and healthy cells (Tacar et al., 2013). Therefore, current therapeutic practices have switched from single treatment applications to multimodal synergism involving a combination of surgical intervention, chemotherapy, radiotherapy, and immunotherapy (Morani and Rane, 2024). These limitations often result in adverse health outcomes and increased treatment costs. To address these challenges, nanotechnology has emerged as a promising approach that complements multimodal cancer therapy while providing a versatile platform for theranostic applications (Medapati, 2025). Nanotechnology-based drug delivery systems, such as liposomal formulations of doxorubicin, have demonstrated improved pharmacokinetics, enhanced bioavailability, and reduced systemic toxicity through efficient drug encapsulation and targeted delivery (Gabizon et al., 2025). These nanocarriers protect the therapeutic agents during circulation and facilitate their accumulation at tumor sites. Furthermore, nanotechnology has enabled the development of multifunctional systems integrating therapeutic and diagnostic capabilities. Such multimodal nontherapeutic platforms combine treatment with imaging techniques, including magnetic resonance imaging (MRI), positron emission tomography, and photoacoustic imaging, to enable precise tumor targeting and real-time monitoring (Venturini et al., 2025). These systems also incorporate targeting ligands, such as prostate-specific membrane antigen (PSMA), for enhanced selectivity toward tumor cells and the tumor microenvironment. Unlike unimodal therapies, multimodal nanotherapy involves integrated and multifunctional approaches executed in a controlled sequential manner by combining therapy with diagnostics (Omidian and Gill, 2025). One example of such therapy is the PSMA ligand-4 (PLZ-4) nanoporphyrin platform, where chemotherapy, photothermal therapy (PTT), and photodynamic therapy are combined in a single system to enhance tumor inhibition (Lin et al., 2016). In the case of drug resistance, gene regulation combined with phototherapy nanoparticles containing photothermal agents to deliver siRNA have been reported (Meng et al., 2013). Guided therapies combining magnetic nanoparticles and MRI with chemotherapy have also been reported (Najafi et al., 2026). Thus, nanoparticles or similar therapeutic agents have been clinically used in precision oncology for targeted cancer therapy to enhance drug penetration, delivery, and imaging.

In parallel with scientific progress, the global cancer therapeutics market has experienced substantial growth fueled by the increasing disease burden, rising healthcare expenditures, and continuous pharmaceutical innovation. Nanotechnology has also played a vital role in this expansion as several nanomedicine-based formulations have been successfully translated into clinical practice. Some notable examples of such formulations include PEGylated liposomal doxorubicin (Doxil®) and albumin-bound paclitaxel (Abraxane®), which have demonstrated improved efficacy and safety compared to conventional formulations. Moreover, regulatory authorities like the United States Food and Drug Administration (USFDA) and European Medicines Agency (EMA) have established frameworks to facilitate the commercialization and approval of nanotherapeutics. However, the main challenges to these efforts include large-scale manufacturing, cost-effective production, long-term stability and safety, and regulatory standardization, which have continued to limit the widespread clinical translation of nanotechnology-based systems. These factors highlight the need for integrated approaches bridging scientific innovation with market and regulatory considerations in cancer therapeutics. Therefore, we discuss the applications of nanotechnology in bridging standard treatments as multimodal approaches, challenges and limitations to such applications, and advancements to maintaining the application status in the commercial market. Moreover, we compare the previously used traditional unimodal and multimodal therapies with nano-unimodal and nano-multimodal therapies as well as their status in the commercial market as stable therapeutics against cancer. By integrating scientific advancements with clinical and market perspectives, this review seeks to bridge the gap between research-based innovations and real-world applications of cancer therapeutics.

2 Classification and functional roles of nanotechnology in cancer therapeutics

Nanoparticle systems are classified into organic, inorganic, and hybrid types based on their functional contributions (Bhatia, 2016). Organic nanoparticles are based on carbon or biological materials such as lipids, polymers, and proteins that are suitable for drug encapsulation, sustained release, and surface functionalization (Yhee et al., 2014); these include liposomes, polymeric nanoparticles, dendrimers, micelles, fluorescent organic nanoparticles, and protein-based nanoparticles. Inorganic nanoparticles include metals, metal oxides, silica, or carbon-based inorganic structures that are generally used in imaging, PTT, and biosensing (Pugazhendhi et al., 2018); these include gold, magnetic, and mesoporous silica nanoparticles as well as quantum dots and carbon nanotubes. Hybrid nanoparticles combine both organic and inorganic components in a single platform (He et al., 2015); these include lipid–polymer hybrids and PEGylated metal–organic frameworks, whose types and therapeutic roles dictate their utilization in targeted delivery for enhanced drug accumulation, controlled drug release, and multimodal enhancement.

Based on their functional roles, hybrid nanoparticles may be classified as targeted-delivery-based active and passive particles (antibody-conjugated nanoparticles, gold particles coated with folic acid, and Abraxane—albumin-bound paclitaxel), stimulus-responsive particles (pH-sensitive liposomes), hyperthermia or ablation particles (gold nanorods), molecular sensors (nanowires that can detect single-cancer-specific molecules), and biosensors (nanoshells whose surfaces have enhanced Raman scattering properties). Based on applications, hybrid nanoparticles can be classified as those used in drug delivery systems (PEGylated liposomes like Doxil), imaging and diagnostics (supermagnetic iron oxides for MRI), and tissue engineering (carbon nanotube scaffolds for bone or nerve regeneration) (Bhatia, 2016). Active nanoparticles are often functionalized using ligands having receptor specificity, while passive nanoparticles accumulate in tumors primarily through the enhanced permeability and retention (EPR) effect (Clemons et al., 2018). The stimulus-responsive particles release drugs in response to internal or external stimuli, while the hyperthermia or ablation nanoparticles are capable of energy conversion for destroying cancer cells using heat (MacEwan et al., 2010). Nanostructure-based sensing of cancer-based biomolecules has been used to create sensing platforms that can detect different types of cancers with high sensitivity.

3 Evolution from conventional to nano-enabled multimodal platforms

Several nanodrugs have been used to assist with and alter the risk factors in cancer therapy as complementary strategies. Doxil is one such paradigmatic nanodrug that is capable of reducing the severe cardiotoxicity associated with conventional doxorubicin therapy in the treatment of breast cancer (Gabizon et al., 2025). Given the hazard ratio of ∼3.16, patients (receiving dose levels above 450 mg/m²) treated with liposomal doxorubicin were more than three times less prone to experiencing cardiotoxicity than those administered free doxorubicin. The polydopamine–diethyl-maleate–iron (III) oxide@membrane (PDA-DEM-Fe₃O₄@M) nanocarrier developed for tumor therapy is a multifunctional nanomedicine combining PTT and chemotherapy with magnetic and tumor cell membrane-targeting capabilities to yield stronger inhibition of tumor cells and is more cytotoxic compared to single modalities (Zhang et al., 2024). The cell viability reduced to ∼19.21% in the PDA-DEM-Fe₃O₄@M + near-infrared (NIR) light group (combined tumor cell membrane targeting, PTT, and chemotherapy) compared to ∼54.03% for the PDA-DEM + NIR, ∼48.16% for the PDA-DEM-Fe₃O₄ + NIR (PTT or chemotherapy alone), and ∼81.92% for the PDA-DEM-Fe₃O₄@M without NIR groups. This highlights the synergistic and enhanced cytotoxic effects of multifunctional nanomedicine. Alginate hydrogel integrated with gold nanoparticles and cisplatin for trimodal therapy (PTT, chemotherapy, and radiotherapy) exhibited better anticancer effects than monomodal or dual-mode treatments by increasing the intracellular reactive oxygen species (ROS) levels by 4.4 times and upregulating apoptotic gene expression (Alamzadeh et al., 2020).

The progression of cancer therapy from traditional to advanced nano-enabled approaches have been further upgraded with multimodal strategies (Mousavi-Kiasary et al., 2025; Sandbhor et al., 2024; Zachou et al., 2025). Multimodal nano-platforms function as adjunct technologies integrating conventional treatment rather than replacing them to create synergistic therapeutic outcomes. From low specificity, high toxicity, and limited integration to enhanced specificity, therapeutic synergy, and resistance management with enabled theranostic applications and stimulus-responsive drug release, multimodal nanoparticles represent the most advanced and multifunctional therapeutic strategy (Figure 1; Table 1).

TABLE 1. Comparative analysis of different therapies operating as unimodal and multimodal strategies with and without nanotechnology.

4 Commercial distribution of nanotechnology in the cancer treatment market

The global nanotechnology-enabled cancer therapeutics market has experienced substantial growth driven by the increasing cancer incidence, technological advancements, and investments in targeted drug delivery systems. The global oncology therapeutics market has been valued at over 105 billion USD in recent years and is projected to increase at a compound annual growth rate of 16% from 2026 to 2034 (Siegel et al., 2025; Fortune Business Insights, 2025). Within the healthcare sector, oncology is a dominant segment with a market share of 43.5%, followed by infectious diseases at 18% (mRNA lipid nanoparticle vaccines for COVID-19) (The Business Research Company, 2025), cardiovascular conditions at about 12% (nano-coatings for stents and targeted delivery), and neurological diseases at 8% (blood–brain barrier); most nanomaterials used in these fields for drug delivery and therapeutic interventions are lipid-based, polymeric, or inorganic in nature (SkyQuest Technology, 2025). From a regional perspective, North America is the most advanced in terms of research and development and occupies the largest market share, while Japan, China, and India account for the highest market presence in the Asia-Pacific region owing to increased government funding, pharmaceutical manufacturing capabilities, and healthcare demand, as well as the large population base (Fortune Business Insights, 2025). The largest manufacturers in these regions are Pfizer Inc. (United States; lipid nanoparticles, mRNA vaccines, and targeted cancer therapies), Takeda Pharma (Japan; nano-targeted therapies for oncology and rare diseases), Taiwan Liposome Co. (Taiwan; liposomal technology for pain management and oncology), and CSPC Pharmaceutical (China; liposomal doxorubicin and generic nano-formulations). Irinotecan hydrochloride liposome injection (II) and Lipusu® are approved nanomedicines in China, while Doxil®, Abraxane®, Vyxeos®, and Onivyde® are some of the nanomedicines or key clinical candidates approved by the USFDA and EMA in recent years (2020–2025).

In terms of material classification, organic nanocarriers including liposomes and polymer–drug conjugates account for the largest market shares of 40%–45% and 25%–30% (Doxil®, Vyxeos®, and Abraxane®), respectively, because of their superior biocompatibility and regulatory acceptance (Fortune Business Insights, 2025; Grand View Research, 2023). Inorganic nanoparticles based on metals and metal oxides [gold, iron, and hafnium (Densify)] occupy 10%–15% of the market share, while micelles and dendrimers occupy approximately 10% of the market share owing to their regulatory complexity and limited long-term toxicity data (Roots Analysis, 2023). In terms of patient requirements, nanomedicines occupy 55.95% market share in therapy, 25% share in diagnostics, and 19% share in regenerative medicine and implants. These indicate that pharmaceutical industries primarily focus on improving drug delivery and reducing systemic toxicity.

Several commercially successful nanomedicines can be used to illustrate the current market trends. Abraxane is built on the albumin-based delivery system and is used to deliver high doses of paclitaxel directly to tumors without any allergic reactions. It occupies the largest share in the oncology market at 22% and is used in the treatment of breast, lung, and pancreatic cancers (Bristol Myers, 2024). Doxil or liposomal doxorubicin occupies about 18% of the market share (worth 1.5 billion USD in 2025) for oncological therapeutics and has been used in patients with ovarian cancer and multiple myeloma (Towards Healthcare, 2024); the PEGylated coating of this drug assists circulation in blood for longer durations and leakage into tumor tissues via the EPR effect, thereby protecting the heart from toxicity. Onivyde is an irinotecan liposomal drug that remains stable in the bloodstream and occupies about 9% of the market share; it is used in the treatment of pancreatic cancer by ensuring that the drug reaches the tumor location at a high concentration (Ipsen Pharma, 2024). Vyxeos occupies approximately 6% of the market share and is a combination nanomedicine consisting of daunorubicin and cytarabine liposomes in a fixed ratio of 5:1 for the treatment of acute myeloid leukemia (Jazz Pharmaceuticals, 2024). Densify inorganic nanoparticles are the first-in-class radio enhancers that assist with drug delivery and in radiotherapy (Nanobiotix, 2024).

5 Principal competitors and synergistic integration of nanotechnology

Although nanotechnology-based systems are a dominant force in cancer therapeutics, they have a few principal competitors; these include antibody–drug conjugates (molecular-level precision without carrier shell complications), cell-based therapies (biological method), microdevice delivery (long-term, site-specific dosing without systemic circulation), and viral vectors (natural nanoparticles that are more efficient at entering cells) (Nature Reviews Drug Discovery, 2025). Different tools like biomimetic engineering, genetic reprogramming, and molecular hijacking have been combined to enhance multimodal treatments by targeting the receptors and surviving hypoxic centers of tumors, finding hidden metastases to completely remove damaged organelles or cell aggregates, and preventing damage from side effects (Mengyuan et al., 2024). These include debulking the primary tumor with surgery, followed by lymphodepletion and CAR-T cell therapy in leukemia, lymphoma, and multiple myeloma; gene editing is performed to combat tumor resistance using CRISPR-Cas in sickle cell disease and beta thalassemia for gene knockout; cellular reset is performed to aid treatment availability using proteolysis targeting chimeras during neoadjuvant therapy in breast cancer for driver protein degradation and tumor shrinkage (approved up to phase III human trials); molecular glues such as lenalidomide have been used in the treatment of multiple myeloma, while genetically engineered anaerobic bacteria and T-VEC-based oncolytic virotherapy have been used against melanoma (June and Sadelain, 2024; Békés et al., 2022; Conry et al., 2024; Słabicki et al., 2023; Nature Biotechnology, 2024).

Even with the advancements achieved, limitations have been observed that restrict the application of new modern tools; nanotechnology bridges this gap by enabling nanocarriers to transport drugs and providing immune clearance to reach the tumor. Lipid nanoparticles act as carriers for CRISPR Cas-9 and enable targeted delivery to the liver cells (primarily hepatocytes) without protecting them from nucleases or immune clearance (Nature Biotechnology, 2024). Lipid nanocoatings (lipid polymer surface modifications) have also been used to cloak oncolytic viruses by neutralizing the antibodies generated by the immune system in response to viruses (Nature Biotechnology, 2024).

6 Nanotechnological advancements in cancer therapeutics

Nanotechnology is supported by various fields like material sciences, information technology, and energy and environment sciences. While material sciences focus on the engineering of nanomaterials with specific physiological properties (size, morphology, and surface chemistry), information technology supports imaging and diagnostics through the integration of advanced imaging and artificial intelligence-based monitoring; the unique physical properties afforded by these fields allow energy convergence (e.g., NIR into heat) and help maintain the laws of environment and biosafety through a regulatory framework supported by research studies and advancements to build new paths for nanotechnology (Yusuf et al., 2023; Chow, 2025; Kurul et al., 2025; Sarma et al., 2021). In the surface engineering of polymeric nanocarriers, functional groups like polyethylene glycol (PEG) and charged moieties can be modified to improve drug loading, stability, and targeting. Smart polymeric nanoparticles can be engineered to respond to stimuli (pH and enzymes) and triggered to release only when in desired tumor environments. Chemical modifications of the surface groups in dendrimers enable controlled release, often through stimulus-responsive links (e.g., pH-sensitive bonds); these design features improve the therapeutic efficacy while reducing systemic toxicity compared to conventional drugs.

One of the recent advancements in material synthesis is phase-change and atomic-level material engineering for synthesizing microscopic phases of inorganic nanoparticles. The sub-stoichiometric molybdenum oxide (Mo₈O₂₃) oxygen-deficient nanoparticle structures contain atomic defects that alter the electronic properties of the material (Medapati, 2025). These were engineered to force a phase transition using pulsed laser ablation in liquid (PLAL). Upon exposure to NIR light, these particles convert the absorbed energy into heat to trigger hyperthermia in the cancer cells. The ability of molybdenum oxide to transition between different atomic arrangements through adjustment of the laser parameters via PLAL, which allows synthesis in a liquid medium in the absence of toxic chemical surfactants, resulted in the formation of highly biocompatible nanoparticles for medical use. However, this technology still remains at the preclinical research stage. Similarly, molybdenum oxide nanoparticles have been integrated with cancer-associated fibroblast-targeted ferritin carriers to create a multimodal therapeutic approach called nano-photoimmunotherapy (Medapati, 2025). This stimulus-responsive smart structure works with the extracellular matrix produced by the cancer-associated fibroblasts and often leads to resistance toward chemotherapy and immunotherapy. Upon photothermal heat generation, the particles encapsulated in the ferritin-based nanocages were observed to conjugate with the anti-FAP antibodies to deplete the cancer-associated fibroblasts, dismantle the tumor shield, and reduce collagen density by 76% along with an 18-fold increase in drug penetration. Other advancements in the field include emerging nanomaterial classes, such as heavy-metal-free quantum dots to overcome the toxicity caused by cadmium-based quantum dots. These were developed as carbon, silicon, and graphene quantum dots to maintain high-resolution imaging capabilities, which have led to 70% mRNA inhibition in gene silencing. Another type of nanomaterial, namely, anodic alumina nanotubes, was electrochemically engineered using pulse anodization as an alternative to carbon nanotubes to ensure controlled drug release (Wang et al., 2024).

7 Challenges and limitations

Although nanotechnology has become a bridge to address the gap in cancer therapeutics, it has several limitations and critical challenges, including technical, regulatory, and biological barriers, as well as toxicity. In immunogenicity and immune clearance, foreign bodies are recognized by the immune system that can trigger allergic reactions and reduce therapeutic effectiveness. Rats pretreated with PEG-based pharmaceutical excipients (F68 and F167) containing PEG segments showed anti-PEG antibody induction, accelerated clearance, and reduced antitumor efficacy (Miao et al., 2023); here, F68 caused 3.8-fold and 32.2-fold increases in anti-PEG IgG and IgM levels, respectively, while F127 caused 7.7-fold increase in IgM. The circulation of PEG liposomal nanoparticles was also shortened, and about 33% antitumor reduction levels were observed. Variability in the EPR effect due to tumor vasculature and microenvironment has also been reported, which creates uneven accumulation of the nanomedicine as it relies on passive targeting of tumors. A noninvasive imaging method like dynamic contrast-enhanced MRI was used with a nano-sized contrast agent in three different ovarian cancer xenografts, where some tumors were observed to leak nanoparticles with concentration variations (Nomani et al., 2024). Stimulus-responsive nanoparticles and tumor microenvironment-modifying systems, including cancer-associated fibroblast-targeted nanotherapies, aim to overcome these limitations by improving drug penetration beyond passive accumulation mechanisms.

Significant challenges may arise in terms of both clinical application and regulatory approval owing to drug toxicity and safety concerns in response to interactions with the human body, which can be handled using nanocarriers. Although Doxil is effective in cases where conventional doxorubicin is used, it has been reported for its side effect of hand-foot syndrome (palmar-plantar erythrodysesthesia or PPE) and 4.5 months of median progression-free survival (O’Brien et al., 2004). During the phase III trial of PEGylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin as a first-line treatment of metastatic breast cancer, risk of cardiotoxicity was observed to be higher with the conventional treatment, while PPE (48%), mucositis, and stomatitis were observed to occur more frequently with the PEGylated liposomal doxorubicin (O’Brien et al., 2004). The authors also noted a partial response rate of 6% with no translation to meaningful tumor regression for most patients.

Two trials involving GRT-R901 (chimpanzee adenovirus prime) and GRT-902 (self-amplifying RNA boost in lipid nanoparticles) have been reported recently for patients with metastatic non-small cell lung cancer, microsatellite-stable colorectal cancer (MSS-CRC), gastroesophageal adenocarcinoma, and urothelial cancer, with phase 1/2 involving GRT-C901/GRT-R902 (multitumor) and GRANITE phase 2/3 involving MSS-CRC and GRT-R902 (Hecht et al., 2022; Palmer et al., 2022). The outcomes of these trials showed low objective response rates with low tumor shrinkage (∼8% partial responses and ∼52% stable disease) and medium levels of improvement.

Long-term nanotoxicity and bioaccumulation are also important concerns when using nanomedicines. In the case of imaging and diagnostic applications, gold and silver nanoparticles show increased toxicity that could lead to long-term accumulation, chronic organ exposure, and regulatory scrutiny owing to their non-biodegradability (Alarcon et al., 2023). One study reported long-term retention of gold nanoparticles in the liver without clearance for at least 47 d, which could become a central concern with nanotoxicity. Thus, the challenges and limitations also hinder the utility of nanomedicines by placing restrictions on exploring their further applications as well as commercial positioning and market value.

8 Conclusion

The progression of unimodal traditional cancer therapeutics to multimodal therapies and nanotechnology-based multimodal treatments is the transformation trend observed in the therapeutics market. Nanotechnology has transformed unimodal therapies into nano-assisted cancer therapies, where different classes of nanoparticles have been used to encapsulate and deliver drugs to the target tumor sites. These nano-based therapeutics have overcome the limitations of traditional and conventional cancer therapies, such as toxicity, drug resistance, and biological barriers, by escaping the tumor mechanisms and delivering potent treatments to the tumor locations directly to ensure precise destruction; these have ensured a definite status for nanomedicines in the cancer therapeutics market. Nanotechnology has attained commercial status in oncology and therapeutics through progress achieved with material sciences, information technology, artificial intelligence-driven optimization, and real-time monitoring while integrating competitor strategies as cooperators in cancer therapy. Thus, nanotechnology-based medicines as multimodal treatment options have become one of the most progressive advancements in cancer therapeutics and emerged as a bridge to de-elevate the global health burden of cancer.

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Footnotes

Edited by: Bwalya Angel Witika, Sefako Makgatho Health Sciences University, South Africa

Reviewed by: Jiale Qu, Binzhou Medical University, China

Anu Radha Pathania, Parul University, India