Photo-triggered and magnetically guided nanosystems for precision drug transport: architecture development, spectral analysis and release behavior

1 Introduction

Among clinically prevalent malignant tumors, hepatocellular carcinoma (HCC) remains one of the most aggressive malignancies worldwide, with particularly high morbidity and mortality rates in Asian populations (Cho et al., 2023; Han et al., 2024; Sim et al., 2024). Despite the availability of various chemotherapeutic agents, treatment outcomes are often compromised by poor drug distribution, limited selectivity, and severe systemic toxicity. Daunorubicin (DNR), a widely used anthracycline, exhibits potent anticancer activity against leukemia and other malignant diseases (Fujiwara et al., 2022; Osoro et al., 2022; Rai and Satija, 2023); however, its clinical utility for HCC is hindered by rapid metabolic conversion into cardiotoxic derivatives within hepatic tissue. Recent studies have demonstrated that coadministration of DNR with metabolic modulators and smart carriers can partially alleviate this issue, prompting renewed interest in exploring DNR-based therapeutic strategies for liver cancer (Li et al., 2014; Vladu et al., 2022; Choi et al., 2022; Liu et al., 2022).

Nonetheless, the intrinsic limitations of conventional DNR administration, including insufficient tissue retention, low bioavailability, and lack of targeted release, underscore the urgent need for smartly designed drug delivery systems (Djayanti et al., 2023; Gupta et al., 2023). Although lipid-based nanocarriers and polymeric vehicles have been extensively studied, their performance is often limited by unstable loading capacities or poor controllability (Fathy et al., 2023). By contrast, mesoporous silica materials, especially MCM-41, offer highly ordered pore networks and versatile surface chemistry, making them attractive candidates for constructing advanced, stimuli-responsive nanoplatforms (Djayanti et al., 2023). When combined with external triggers such as magnetic fields or irradiation, these nanoscale systems can potentially achieve high loading efficiency, active targeting, and programmable drug discharge (Adam and Mertz, 2023; Qi et al., 2023).

In the present work, we set out to integrate these key features into a single multifunctional nanocomposite. Superparamagnetic Fe₃O₄ nanoparticles were selected as the magnetic core to enable external field-guided accumulation at diseased sites. The core was encapsulated within an MCM-41 shell to provide abundant pore volume for DNR loading, and a light-responsive organic ligand was grafted onto the pore entrances to serve as a controllable gate for on-demand drug release. The resulting composite was systematically characterized and evaluated for its biocompatibility and in vitro drug-release behavior. Our findings demonstrate that this dual-stimuli-responsive system holds promise as an emerging therapeutic approach for precise HCC treatment.

2 Experimental details

2.1 Starting materials

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) was acquired from Beijing Suolaibao Technology. Benzophenone hydrazine was sourced from Shanghai Macklin. (phosphate buffered saline) PBS, Dulbecco’s modified Eagle’s medium (DMEM), trypsin (0.25% in EDTA) and fetal bovine serum (FBS), were supplied by Wuhan Boside Biological Technology. tetraethoxysilane (TEOS, analytical grade), poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSS:MA, 1:1), and (3-chloropropyl)trimethoxysilane (CPTS, with a purity greater than 98%) were all obtained via Sigma-Aldrich. Daunorubicin hydrochloride (DNR∙HCl, with a purity exceeding 98%) and the organic ligand (2-bromo-9-fluorenone) were procured from Chengdu Desaier Bio-Tec. Dichloromethane (DCM), absolute ethanol, ethylene glycol, and aqueous ammonia (NH₃·H₂O, 28 wt%) were purchased from Qingdao Haiyang Chemical Co., Ltd. Cetyltrimethylammonium bromide (CTAB, analytical grade), FeCl₃∙6H₂O (analytical grade), and NaOH were bought from Huai’an Kelong Chemicals. A solution containing penicillin and streptomycin, with concentrations of 10,000 units per mL of penicillin and 10,000 μg per mL of streptomycin was used for cell culture. All solvents and reagents obtained from these companies were utilized directly without undergoing any further purification.

2.2 Characterization instruments

Particle size and hydrodynamic diameter were determined using dynamic light scattering (DLS, Zetasizer Nano ZS, Malvern). Morphological analysis was performed using transmission electron microscopy (TEM, JEM-2010, JEOL) and scanning electron microscopy (SEM, SUPRA 55, ZEISS). X-ray diffraction (XRD) patterns were collected using an X-ray diffractometer (Rigaku Multiflex, λ = 1.5418 Ǻ). For the IR analysis, the KBr protocol was implemented using a Perkin-Elmer Spectrum-100 FT-IR spectrometer. The magnetic properties were investigated using a sample magnetometer (MPM5-XL-5, Quantum Design). The pore size and volume were evaluated by N₂ adsorption/desorption experiments, with subsequent calculations performed using the BJH method via a Nova-l000 analyzer. In MTT assay, the optical density (OD) values at a wavelength of 490 nm were measured using a microplate reader (Synergy H1, Biotek). The concentration of drug molecules was determined using UV-Vis and UV-Vis-NIR spectroscopy (UV-1900i, Shimadzu). The Daunorubicin loading on the final nanocomposite was quantified through thermogravimetric analysis (TGA, STA-6000, Perkin-Elmer) under unspecified conditions, with all operations carried out at room temperature.

2.3 Synthesis of photo-triggered ligand

The C=N double bond in imine compounds is known to undergo reversible configurational isomerization under light irradiation, enabling applications in photoresponsive systems (Wu and Greenfield, 2024). In this study, this property was exploited to construct a photosensitive gating ligand. Briefly, to a round bottom flask with 1.56 mL of hydrazine hydrate and 50 mL of ethanol was added 4.5 g of 2-bromo-9-fluorenone. The reaction mixture was heated to reflux and maintained for 5 h. Then quenched the reaction by cooling to room temperature. Filtered the solution to obtain yellow needle-like crystals of photosensitive molecule as 2-bromo-9-fluorenone hydrazone. ¹H-NMR (CDCl₃): δ 8.05 (s, 1H), 7.85 (s, 1H), 7.74 (d, 2H), 7.6 (d, 1H), 7.36 (m, 2H), 6.51–6.43 (d, 2H).

2.4 Synthesis of photo-triggered & magnetically guided nanocarriers and their precursor composite

The final nano magnetic response & light-triggered nanocomposite for drug loading was denoted as BrBen@M41@Fe₃O₄, highlighting its outermost light-responsive organic ligand as well as the inner core responsible for drug loading and magnetic guidance. And was prepared by the following steps.

2.4.1 Synthesis of Fe₃O₄ nanoparticles

Common methods for synthesizing superparamagnetic nanoscale Fe₃O₄ include hydrothermal synthesis and non-aqueous methods (Masud et al., 2019). To facilitate easier surface modification of the prepared Fe₃O₄, this study adopted the former procedure of the reported literature (Wu et al., 2015).

80 mL of the ethylene glycol was added into a beaker, then weighed out 2 g of PSS:MA (1:1) and slowly add it in portions to the beaker. Continuously stirring during the addition to prevent the PSS:MA (1:1) from agglomeration. Once all the PSS:MA (1:1) had been added, subject the mixture to ultrasonic oscillation until it becomes clear and transparent. Subsequently, 4.32 g of FeCl₃·6H₂O was added and dissolved by ultrasonication, followed by the addition of 6 g of anhydrous sodium acetate. The resulting solution was transferred into a Teflon-lined autoclave and heated at 197 °C for 4 h. After cooling to room temperature, the black precipitate was magnetically separated, washed repeatedly with ethanol and deionized water, and dried under vacuum.

2.4.2 Preparation of SiO₂- and MCM-41-coated Fe₃O₄

Silica coating was performed according to literature procedures (Soares da Silva Burato et al., 2020). Dried Fe₃O₄ nanoparticles (0.16 g) were dispersed in a mixture of ethanol (40 mL), water (2 mL), and NH₃·H₂O (2 mL) and sonicated for 15 min. Subsequently, under continuous stirring combined with ultrasonication, a tetraethoxysilane solution (prepared by dissolving 0.5 mL TEOS in 10 mL EtOH) was slowly introduced via syringe over a period of 30 min. After an additional 1 h, the product was magnetically collected, washed, and dried.

For the preparing of MCM-41 molecular sieve coating modified Fe₃O₄ nanoparticle (denoted as M41@Fe₃O₄), TEOS was then slowly hydrolyzed once again. At this point, with the assistance of the template agent CTAB and stronger basic condition, TEOS will form MCM-41 molecular sieves on the silica-coated iron cores for drug loading purposes (Huang et al., 2020).

To a solution of 50 mL H₂O containing 1.46 g CTAB, 1 g NaOH and 0.1 g SiO₂-encapsulated Fe₃O₄ particles was added. Disperse the mixture by ultrasonication for 10 min. TEOS (0.3 mL total) was added in 50 μL increments at 5-min intervals under ultrasonication. Continue ultrasonic treatment for an additional 60 min, then the product was collected magnetically. The above product was then transferred into a solution containing 30 mL of absolute EtOH and 4 mL of concentrated hydrochloric acid, to remove the CTAB as template, yielding M41@Fe₃O₄.

2.4.3 Surface functionalization with photo-responsive ligand

The photosensitive molecule 2-bromo-9-fluorenone hydrazone was finally connected to the silane coupling regent (3-chloropropyl) trimethoxysilane. 0.5 g M41@Fe₃O₄ was dispersed in a solvent mixture consisting of 5 mL of (3-chloropropyl) trimethoxysilane and 75 mL of anhydrous toluene, facilitated by ultrasonication. The mixture was subsequently heated to reflux and maintained for 8 h. The reaction was terminated by cooling the system to room temperature, followed by thorough rinsing of the resulting product, designated as CPTS @M41@Fe₃O₄, with EtOH and water. Subsequently, 0.25 g of CPTS@M41@Fe₃O₄ and 0.5 g of benzophenone hydrazine derivative were added to a round-bottom flask in 100 mL DMF. The mixture was ultrasonicated 30 min to ensure homogeneity, then was heated to reflux for 8 h. The reaction was quenched by cooling to r.t., and the final product, named BrBen@M41@Fe₃O₄, was rinsed sequentially with ultrapure water and ethanol. The product was then dried under vacuum at 50 °C overnight.

2.5 Drug molecular loading feature of BrBen@M41@Fe₃O₄

In this research, the peak absorbance of 2-bromo-9-fluorenone hydrazone was first studied. Then a 310 nm LED light source was used when loading the testing drug molecule to initialize the flipping of the photo-triggered ligand. 20 mg BrBEN-M41-Fe₃O₄ was added to a quartz test tube with 3 mL DNR (20 mg/mL). Then, the mixture was subjected to continuous light exposure (310 nm) and agitation for 12 h to establish equilibrium between DNR adsorption and desorption. The DNR-loaded nanoparticles (DNR@M41@Fe₃O₄) were magnetically separated, washed, and analyzed by TGA. The drug loading efficiency was determined to be 1.61 wt%.

2.6 Release Kinetics study of DNR@M41@Fe₃O₄

Drug release experiments were conducted under light (310 nm) and dark conditions. DNR@M41@Fe₃O₄ (5 mg) was dispersed in 5 mL PBS (pH 7.4) and stirred continuously. Aliquots were collected at predetermined time intervals and analyzed at 480 nm using UV–Vis spectroscopy. A maximum release difference of approximately 58% was observed between irradiated and non-irradiated groups.

2.7 Biocompatibility of BrBEN@M41@Fe₃O₄

To investigate potential off-target cytotoxicity of daunorubicin-loaded nanocarriers during chemotherapy, we selected SMMC-7721 human hepatocellular carcinoma cells (obtained from the Shanghai Cell Bank, Chinese Academy of Sciences) for our study. The biocompatibility profile of BrBEN@M41@Fe₃O₄ nanocomposites was evaluated using the MTT assay (He et al., 2018; Krasley et al., 2024; Ye et al., 2020). Cells were cultured in DMEM supplemented with 10% FBS and 1% penicillin–streptomycin. Cells were seeded in 96-well plates (5 × 10³ cells/well) and treated with varying concentrations of BrBen@M41@Fe₃O₄ (concentrations sequent as 1.562, 3.12, 6.25, 12.5, 25.0 and 50.0 μg/mL and the entries was marked as 1 to 6 in Figure 10) for 24 h. Cell viability was quantified by measuring absorbance at 490 nm after MTT incubation.

2.8 Statistical analysis

All experiments were performed in triplicate (n = 3), and data are presented as mean ± standard deviation (SD). Statistical analyses were conducted using GraphPad Prism 10.6. Differences among multiple groups were analyzed using one-way ANOVA followed by Tukey’s multiple comparisons test. A p-value <0.05 was considered statistically significant. Statistical comparisons were performed between the treated groups (cells incubated with different concentrations of the drug carrier) and the control group (cells without any treatment).

3 Results and discussion

3.1 Design and synthetic protocol for nanocomposite: BrBEN@M41@Fe₃O₄

The overall synthetic strategy for BrBEN@M41@Fe₃O₄ is schematically illustrated in Scheme 1. Superparamagnetic Fe₃O₄ nanoparticles were first prepared via a hydrothermal reaction using FeCl₃·6H₂O as the iron precursor, yielding water-dispersible magnetic cores. Subsequently, a mesoporous silica shell (MCM-41) was constructed on the surface of the Fe₃O₄ cores to provide abundant pore volume for drug loading. Finally, photo-responsive organic ligands were covalently anchored within the mesoporous channels to endow the nanocarrier with light-triggered gating functionality. Through this stepwise assembly, a multifunctional drug delivery system capable of magnetic guidance and light-controlled drug release was successfully obtained.

3.2 Size and dispersion of nanocomposite

The size of the final nanocomposites was first studied by a dynamic light scattering instrument (DLS), and the corresponding size are summarized in Figure 1 and Table 1. The average size of the superparamagnetic Fe₃O₄ core (Figure 1; Table 1) is about 280 nm with a narrow PDI (far less than 0.3), showing that the nanoparticles prepared in this experiment exhibit high uniformity. After the Fe₃O₄ core was modified and covered with SiO₂, the average particle size of the core-shell nanoparticles increased to 331 nm (Figures 1, 2; Table 1). Following the deposition of the MCM-41 mesoporous shell, the final BrBEN@M41@Fe₃O₄ nanocomposites display an average diameter of 353 nm (Figures 1–3; Table 1), increasing to 358 nm after final surface functionalization with the photo-responsive ligand to give BrBEN@M41@Fe₃O₄ (Figures 1–4; Table 1). Based on these values, the thickness of the MCM-41 shell was estimated to be approximately 22 nm. The gradual and consistent increase in particle size at each modification step demonstrates the effective layer-by-layer construction of the multifunctional nanocarrier.

TABLE 1. Size and PDI of nanocomposites.

3.3 Surface and interface features of nanocarriers and their precursors

Scanning electron microscopy (SEM) further corroborated the results obtained from dynamic light scattering (DLS). Moreover, it provided a better morphological understanding of the synthesis process. The initial Fe₃O₄ cores exhibited a rough surface with numerous bumps (Figures 1, 2), which, upon closer inspection, were found to be aggregates of many smaller nanospheres. The size, which was consistent with the DLS measurements, was significantly smaller than 300 nm. After silica coating, a pronounced increase in particle diameter was observed (Figure 2), accompanied by a significantly smoother surface. This morphological change can be attributed to the deposition of an amorphous silica layer that fills interparticle gaps and encapsulates the Fe₃O₄ cores.

Subsequent coating with the MCM-41 molecular sieve further increased the particle size and resulted in an even smoother surface morphology (Figures 2, 3). Notably, after functionalization with CPTS and photo-responsive ligands (BrBEN@M41@Fe₃O₄), no significant changes in particle size or surface morphology were observed (Figures 2–4). This observation suggests that the organic molecules were predominantly grafted within the mesoporous channels rather than contributing to an increase in external particle dimensions, in agreement with the DLS results.

In the final TEM results, a spherical nanoparticle with a distinct core-shell structure can be clearly observed (Figures 2–5). The darker inner portion represents the superparamagnetic Fe₃O₄ core, while the outer layers consist of an amorphous silica shell and a molecular sieve shell.

3.4 Vibrating sample magnetometry (VSM) analysis of superparamagnetic

It can be observed from the VSM hysteresis loops of each sample that both the carriers prepared in this study and their precursors exhibit superparamagnetism, with zero hysteresis loops despite differing saturation magnetization intensities among the three samples (Figure 3). Such nanoparticles can stably exist and disperse in solution in the absence of an external magnetic field, while displaying the characteristics of magnetic particles and being guided to corresponding sites by a magnetic field when applied, thereby enabling the magnetic guidance and targeted delivery of drug molecules with the assistance of drug carriers.

The initially prepared superparamagnetic Fe₃O₄ cores possess a relatively high saturation magnetization intensity, measuring 67.4 emu/g (Figures 1–3). After two coating processes, the values decreased to 37.0 emu/g for SiO₂@Fe₃O₄ (Figures 2, 3) and 32.1 emu/g for BrBEN@M41@Fe₃O₄ (Figure 3), with the latter’s reduction primarily attributed to the decreased proportion of Fe₃O₄ cores which providing superparamagnetism. To better demonstrate the superparamagnetic properties of BrBEN@M41@Fe₃O₄, this study dissolved our nanocarrier in ethanol. It can be observed that, in the absence of an external magnetic field, the carrier can disperse uniformly in the solvent. However, when a magnetic field is applied, it exhibits magnetic behavior and aggregates toward the external magnetic field (Figure 4).

3.5 FT-IR analysis of synthesized nanocomposites and derivatives

The nanocomposites and their derivatives prepared in this study exhibit distinct IR features (Figure 5). Conducting IR analysis on the nanocomposites can better substantiate their structures and the effectiveness of each synthetic step. Firstly, since all the nanocomposites possess superparamagnetic Fe₃O₄ cores, prominent absorption peaks are observed at 3,412 cm^-1 and 634 cm^-1 in their IR spectrum (Figure 5). Literature indicates that these peaks are characteristic of Fe-O bonds (Karimian et al., 2024; Moradi and Abdoli-Senejani, 2023). These features indicate that the Fe₃O₄ core structure remained intact throughout the surface modification processes.

After the Fe₃O₄ cores were modified by coating with silica and molecular sieves, the subsequent compounds all exhibit two additional pairs of peaks around 800 cm^-1 and in the range of 1,083–1,088 cm^-1 (Figure 5), which are attributed to the newly introduced Si-O bonds (Palacios et al., 2025). IR spectra revealed that M41@Fe₃O₄ (with CTAB) exhibits additional peaks at 2,921 cm^-1 and 2,851 cm^-1 due to the alkyl chain of CTAB, while M41@ Fe₃O₄ (without CTAB) and CPTS@M41@ Fe₃O₄ are highly similar and do not show the above two peaks, confirming the removal of CTAB (Figure 5).

Finally, due to the presence of a C=N double bond in the photosensitive molecule 2-bromo-9-fluorenone hydrazone, which provides an IR absorption peak at 1717 cm^-1, the absorption peak of the final carrier BrBEN@M41@Fe₃O₄ shifts from 1,627 cm^-1 to 1,650 cm^-1 (Figures 5, 6) compared to CPTS@M41@Fe₃O₄.

3.6 Structural confirmation of cores in nanocomposites via WAXRD analysis

Wide-angle X-ray diffraction (WAXRD) analysis was performed to confirm the crystalline structure of the magnetic core in BrBEN@M41@Fe₃O₄. As shown in Figure 6, both pristine Fe₃O₄ nanoparticles and the final nanocomposite exhibit nearly identical diffraction patterns. Five characteristic diffraction peaks corresponding to the (220), (311), (400), (440), and (511) planes of inverse spinel Fe₃O₄ were clearly observed in both samples.

The preservation of these diffraction peaks after multiple surface modification steps indicates that the crystalline structure of the Fe₃O₄ core was not altered during the synthesis process. Combined with the FT-IR and VSM results, these findings conclusively demonstrate that the magnetic core of BrBEN@M41@Fe₃O₄ consists of well-preserved superparamagnetic Fe₃O₄.

3.7 Isotherms of nitrogen adsorption and desorption for M41@Fe₃O₄ and BrBEN@M41@Fe₃O₄

The nitrogen adsorption-desorption isotherm curves for ligand-functionalized M41@Fe₃O₄ and M41@Fe₃O₄ are presented in Figure 7. Based on the classification criteria in reference (Huang et al., 2012), both composite exhibit an isotherm pattern consistent with type IV. In conclusion, even after undergoing template extraction, coupling with organic ligands, and additional modification with gating molecules, the M41@Fe₃O₄ still preserves its characteristic hexagonal mesostructure. Nevertheless, following these successive chemical processes, the principal characteristic parameter value of the M41@Fe₃O₄ has experienced a reduction. For the M41@Fe₃O₄ sample, its initial surface area and pore volume were measured at 19.0 m²/g and 0.0188 cm³/g, respectively. After the subsequent reactions, these values had decreased to 16.6 m²/g and 0.0147 cm³/g, correspondingly. This decline is primarily attributed to the partial occupation of the pores and channels within the molecular sieve by organic ligands and photosensitive molecules.

3.8 Procedure for DNR loading and determination of host molecule

The controlled-release behavior of BrBEN@M41@Fe₃O₄ originates from the photo-induced configurational inversion of the hydrazone-based ligand under irradiation at specific wavelengths. This conformational change alters the steric environment within the mesoporous channels, thereby modulating pore accessibility and enabling light-triggered drug release. According to previous reports, the C=N bond in hydrazone derivatives exhibits strong absorption near 300 nm and undergoes photoisomerization upon UV irradiation (Yan et al., 2017). UV–Vis analysis revealed that the synthesized 2-bromo-9-fluorenone hydrazone displays a maximum absorption peak at 292 nm (Figure 8). For experimental convenience, a 310 nm UVB LED light source was therefore selected to induce photoisomerization during drug loading and release studies.

The encapsulation efficiency of host molecule-DNR was evaluated via TGA under an inert nitrogen (N₂) atmosphere, employing a heating gradient of 10 °C/min. Comparative analysis revealed that the DNR@M41@Fe₃O₄) exhibited a 1.61% greater mass loss relative to its none-loaded counterpart (BrBEN@M41@Fe₃O₄) at the terminal temperature (Figure 9). Based on these findings, we conservatively estimate the DNR payload within the carrier system to constitute 1.61% (w/w).

3.9 MTT test of BrBEN@M41@Fe₃O₄ drug carrier’s biocompatibility

Biocompatibility is a fundamental prerequisite for drug delivery carriers. The cytocompatibility of BrBEN@M41@Fe₃O₄ was evaluated using an MTT assay with SMMC-7721 human hepatocellular carcinoma cells. As shown in Figure 10, no significant reduction in cell viability was observed after 24 h of exposure to BrBEN@M41@Fe₃O₄, even at concentrations as high as 50 μg mL^-1. These results indicate that the nanocomposite exhibits negligible cytotoxicity under the tested conditions, demonstrating favorable biocompatibility. Therefore, BrBEN@M41@Fe₃O₄ shows promise as a safe carrier for further drug delivery applications.

3.10 In vitro release and performance

To preliminarily investigate the release behavior of the drug carrier BrBEN@M41@Fe₃O₄ prepared in this project under light stimulation and in the absence of light stimulation, and to pave the way for subsequent cell and animal experiments, a comparative test was conducted in this section using PBS as the medium for the DNR-loaded complex (DNR@M41@Fe₃O₄).As can be seen from Figure 11, during the initial stage of drug release, the drug release rate under light stimulation is significantly faster than that in the absence of light stimulation. From the starting points of the curves, it is evident that the curve under light stimulation has a larger slope, indicating that the release rate under light stimulation is increased than that in the absence of light stimulation within the same time interval. Particularly at the 3-h mark, the DNR concentration increased by 60% compared to the condition without light stimulation. However, as time progresses further, the gap tends to gradually narrow. This is because the rapid drug release in the light-stimulated group leads to a rapid decrease in the concentration difference between the inside and outside of the molecular sieve pores, thereby delaying further rapid drug release. Meanwhile, in the group without light stimulation, the drug is continuously and slowly released, causing the gap between the two to converge in the later stage. Under conditions without light stimulation, the drug is slowly released from the carrier mainly through thermal motion and diffusion. This release mode is relatively slower, with a relatively stable release rate, but the overall speed is slow. Overall, light stimulation has a significant promoting effect on drug release. By optimization of light stimulation conditions, it is possible to regulate the rate and extent of drug release, providing promising starting point for the development of novel light-controlled drug delivery systems.

4 Conclusion

In this study, a multifunctional core–shell nanocomposite, BrBEN@M41@Fe₃O₄, was successfully designed and synthesized by integrating a superparamagnetic Fe₃O₄ core, a mesoporous MCM-41 silica shell, and a photo-responsive hydrazone-based gating system. The Fe₃O₄ core endowed the nanocarrier with efficient magnetic responsiveness, enabling external field–assisted guidance, while the mesoporous silica shell provided abundant pore volume for drug loading and structural stability. The incorporation of photo-switchable ligands within the mesoporous channels further enabled light-triggered regulation of pore accessibility and drug release.

Comprehensive characterization using SEM, TEM, DLS, FT-IR, XRD, VSM, and nitrogen adsorption–desorption analyses confirmed the successful construction of the core–shell architecture and the preservation of superparamagnetic properties throughout successive surface modifications. Drug loading and in vitro release studies demonstrated that daunorubicin could be efficiently encapsulated and selectively released under light irradiation, exhibiting a significantly enhanced release rate compared with dark conditions. In addition, MTT assays revealed negligible cytotoxicity of the nanocarrier toward SMMC-7721 cells, indicating favorable biocompatibility.

In summary, the preliminary results of this study indicate that BrBEN@M41@Fe₃O₄ shows potential as a drug delivery platform. This carrier integrates magnetic targeting and light-controlled release functions, offering an innovative approach for programmable and lesion-targeted drug delivery. However, we must acknowledge that comprehensive evaluation data on the biological activity of this nanocarrier are currently incomplete. Biological activity is a critical indicator for assessing the application potential of drug delivery systems in biomedicine, and an in-depth exploration of its biological activity is of paramount importance for fully validating the effectiveness and safety of this platform. Therefore, in future research endeavors, the focus will be on experiments related to biological activity. Through these experiments, we aim to gain a more comprehensive and in-depth understanding of the biological activity characteristics of this nanocarrier, thereby providing further studies evidence for the practical therapeutic application of the carrier prepared in this work.

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Footnotes

Edited by: Aamir Suhail, Harvard Medical School, United States

Reviewed by: Mary Cano-Sarabia, Catalan Institute of Nanoscience and Nanotechnology (CIN2), Spain

Philip Newton, AstraZeneca, United Kingdom