The development of multifunctional nanocarriers has become a critical focus in cancer therapy, to improve drug selectivity and minimize systemic toxicity. In this study, Fe₃O₄/SiO₂ core–shell nanoparticles functionalized with 3-aminopropyltrimethoxysilane (NH₂) and folic acid (FA) were designed as a dual-targeting system for the delivery of doxorubicin (Dox). The design was informed by a systematic review of literature published between 2015 and 2025 across major scientific databases, highlighting the need for biocompatible, pH-responsive carriers with receptor-mediated targeting. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized as the core, coated with silica, and conjugated with FA to enable folate receptor binding. Structural characterization confirmed the cubic spinel structure of Fe₃O₄ (XRD), with an average particle size of 11 nm (HRTEM) and hydrodynamic diameter of 14 nm (DLS). Magnetic measurements demonstrated strong superparamagnetic properties, supporting potential external guidance. Cytotoxicity was assessed using MTT assays in A549 (lung cancer) and 5637 (bladder cancer) cell lines, showing selective activity against malignant cells. Drug release studies revealed pH-dependent behavior: at pH 5.4, 50% of Dox was released within 4 h and 68.09% over 93 h, compared to 42% and 52.89% at pH 7.4. Kinetic modeling indicated first-order release dynamics. Collectively, these findings demonstrate that Fe₃O₄/SiO₂ coreshell nanoparticles provide a promising platform for targeted and sustained delivery of Dox, offering reduced side effects and enhanced therapeutic potential in cancer treatment. Importantly, this study addresses a pressing challenge in oncology by providing a multifunctional nanocarrier that combines magnetic guidance, folate receptor targeting, and pH-responsive drug release. Such a system not only enhances therapeutic precision but also reduces systemic toxicity, underscoring its potential as a clinically relevant platform for next-generation cancer treatment.
Azari et al. (2026) studied this question.