Magnetic Nanocarriers with ICPTES- and GPTMS-Functionalized Quaternary Chitosan for pH-Responsive Doxorubicin Release

Smart nanocarriers are being increasingly explored to improve the performance selectivity of cancer chemotherapy. Here, two pH-responsive magnetic nanocarriers were developed using quaternary chitosan (HTCC) functionalized with 3-(triethoxysilyl)propyl isocyanate- ICPTES (MNP-HTCC1) or 3-(glycidyloxypropyl)trimethoxysilane-GPTMS (MNP-HTCC2) to form hybrid silica shells on Fe₃O₄ cores. The resulting core-shell nanoparticles (14.5 and 12.5 nm) displayed highly positive zeta potentials (+45.4 to +27.1 mV, pH 4.2-9.5), confirming successful HTCC incorporation and strong colloidal stability. Both nanocarriers achieved high doxorubicin (DOX) loading at pH 9.5, reaching 90% efficiency and a capacity of 154 µg DOX per mg. DOX release was pH-dependent, with faster release under acidic conditions relevant to tumor and endo-lysosomal environments. At pH 4.2, MNP-HTCC1 released 90% of DOX over 72 h, while MNP-HTCC2 released 79%. Release at pH 5.0 was intermediate (67-72%), and moderate at physiological pH (43-55%). All formulations showed an initial burst followed by sustained release. Kinetic modelling (Weibull) indicated a diffusion-controlled mechanism consistent with Fickian transport through the HTCC-silica matrix. Cytotoxicity assays using MCF-7 breast cancer cells revealed greater cytotoxicity for DOX-loaded nanocarriers compared with free DOX, with MNP-HTCC1 showing the strongest effect. Overall, these HTCC-based magnetic nanocarriers offer efficient loading, controlled pH-triggered DOX release, and enhanced therapeutic performance.