APTES-functionalized Gd_0.18Fe_2.82O₄@SiO₂ nanocarrier for magnetothermal-triggered doxorubicin release

Externally regulated and stimuli-responsive drug delivery systems remain of significant interest for improving the controllability of cancer treatment strategies. In this study, APTES-functionalized Gd_0.18Fe_2.82O₄@SiO₂ core-shell nanoparticles were developed as a pH- and magnetically responsive platform for doxorubicin (DOX) delivery. Structural and morphological characterization confirmed quasi-spherical nanoparticles with mesoporous silica shells and satisfactory colloidal stability under physiological conditions. FTIR analysis indicated successful DOX adsorption mediated by electrostatic interactions and hydrogen bonding with amino-functionalized surfaces. The system achieved a DOX loading efficiency of 82.6% at pH 7.4, and adsorption kinetics followed a pseudo-second-order model. In vitro release studies demonstrated pronounced pH-dependent behavior, with enhanced drug release under acidic conditions. Upon exposure to an alternating magnetic field (200 Oe, 450 kHz), efficient magnetothermal heating was induced, enabling rapid and externally regulated enhancement of DOX release. Cytotoxicity assays showed negligible intrinsic toxicity of the unloaded carrier under the tested conditions, while the DOX-loaded nanoparticles induced concentration-dependent cytotoxic effects in HepG2 and MCF-7 cells (IC₅₀ ≈ 50 µg mL^-1 for the carrier, corresponding to ∼2.6-2.7 µg mL^-1 DOX equivalent). AMF-mediated heating resulted in temperature-dependent loss of cell viability, exceeding 90% at 55 °C within 10 min. Overall, the Gd_0.18Fe_2.82O₄@SiO₂/APTES/DOX system demonstrates alternating magnetic field (AMF)-responsive drug release and pronounced temperature-dependent cytotoxicity, supporting its potential for chemo-magnetic cancer treatment.