Synthesis of magnetic porous silica nanoparticles functionalized with folic acid for targeted drug delivery of quercetin

Targeted drug delivery systems offer a promising strategy to enhance anticancer efficacy while minimizing systemic side effects. In this study, a multifunctional nanocarrier based on magnetic mesoporous silica nanoparticles was developed for the targeted delivery of quercetin. Fe₃O₄ nanoparticles were incorporated into mesoporous silica, followed by surface coating with polydopamine, conjugation of folic acid as a targeting ligand, and loading of quercetin. The successful stepwise modification of the nanoparticles was confirmed by FESEM, BET, FTIR, XRD, Zeta potential, PSA, and TGA analyses. The final formulation (Si-Fe-Q-D-F) exhibited a mesoporous structure with reduced pore size and surface area after drug loading and ligand conjugation. In vitro cytotoxicity evaluation using the MTT assay revealed that the drug-free carrier was highly biocompatible, whereas Si-Fe-Q-D-F showed superior anticancer activity against MCF-7 cells, with an IC₅₀ value of approximately 19 µg/mL after 48 h, significantly lower than that of free quercetin (57 µg/mL). The clonogenic assay further showed strong, dose-dependent inhibition of long-term colony formation by Si-Fe-Q-D-F. Moreover, the nanocarrier showed pH-responsive drug release, with accelerated quercetin release at pH 5.0 than at physiological pH. These findings indicate that folic acid-functionalized magnetic mesoporous silica nanoparticles are a promising multifunctional platform for targeted, controlled delivery of quercetin in breast cancer therapy.