Chitosan-coated mesoporous silica nanoparticles for pH-responsive doxorubicin delivery in head and neck cancer

Figures

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  FIGURE 1. Schematic representation of the synthesis route and pH-responsive drug release mechanism of the MSN-DOX@CS nanocarrier. The synthesis involves three sequential steps (Barsouk et al., 2023): preparation of bare mesoporous silica nanoparticles (MSNs) (Mordzińska-Rak et al., 2025), loading of doxorubicin (DOX) into the mesopores, and (Ganesan et al., 2024) coating with chitosan (CS) to seal the pores. The lower panel illustrates the release mechanism: at physiological pH (7.4), the intact chitosan layer keeps the “gatekeeper” closed, resulting in minimal drug release (∼18%). In contrast, at acidic pH (5.5), the protonation of chitosan amino groups (–NH3 +) causes electrostatic repulsion and polymer swelling, opening the gatekeeper and enabling rapid drug release (>76%).

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  FIGURE 2. FESEM image of MSN and MSN-DOX@CS nanoparticles.

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  FIGURE 3. Size characteristics and surface charge (Zeta Potential) of nanoparticles.

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  FIGURE 4. FTIR spectra of bare mesoporous silica nanoparticles (Bare MSN, black), free doxorubicin (Free DOX, red), pure chitosan (Pure Chitosan, green), and the final chitosan-coated doxorubicin-loaded nanoparticles (MSN-DOX@CS, blue). The bare MSN spectrum shows characteristic Si–O–Si stretching bands at 1,080 and 800 cm−1 and O–H stretching at 3,430 cm−1. The free DOX spectrum exhibits diagnostic anthracycline ring peaks, including C=O ketone (1730 cm−1), C=O quinone (1,618 cm−1), aromatic C=C (1,580 cm−1), and N–H bending (1,525 cm−1). The pure chitosan spectrum displays Amide I (1,655 cm−1) and Amide II (1,595 cm−1) bands. The MSN-DOX@CS composite spectrum contains all characteristic peaks of the individual components, confirming successful drug loading and chitosan coating.

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  FIGURE 5. UV-Vis absorption spectra of free doxorubicin (Free DOX, red solid line), the drug-loaded nanocarrier (MSN-DOX@CS, blue solid line), and the empty nanocarrier (MSN@CS, black dashed line) recorded over the wavelength range of 200–650 nm. The free DOX spectrum displays characteristic anthracycline absorption bands at 232, 252, and 290 nm (UV region) and at 480 and 530 nm (visible region). The MSN-DOX@CS composite spectrum exhibits the same absorption features with a slight red shift (∼3 nm; 232 → 235 nm and 480 → 483 nm) and peak broadening, confirming successful drug loading and molecular interactions between DOX and the silica–chitosan matrix. The empty MSN@CS carrier shows negligible absorption across the entire range, demonstrating the absence of interfering chromophores.

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  FIGURE 6. Cumulative release profile of doxorubicin from MSN-DOX@CS nanoparticles in two environments with physiological pH (7.4) and acidic tumor pH (5.5) over a period of 48 h.

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  FIGURE 7. Percentage of HNSCC cell viability after 24 (A) and 48 h (B) of treatment with empty nanoparticles (negative control), free DOX, and MSN-DOX@CS nanoparticles at different DOX concentrations, based on MTT assay (*p < 0.05, statistically significant compared to the control group).

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  FIGURE 8. Cell viability of normal (HaCat) cells after (A) 24 h and (B) 48 h of treatment with empty nanoparticles (MSN@CS), free DOX, and MSN-DOX@CS at different concentrations. The empty carrier showed excellent biocompatibility (>100% viability). Notably, MSN-DOX@CS exhibited significantly reduced toxicity toward normal cells compared to Free DOX (p < 0.05), confirming the selective safety profile of the pH-responsive system.