Combinatorial therapy, Magnetic nanocomposites, Targeted delivery system, pH-responsive, Core-shell structure, Materials of engineering and construction. Mechanics of materials, TA401-492

Designing nanoplatforms that integrate multimodal therapies provides a novel strategy to overcome the shortcomings of conventional single-modal therapy. In this study, a hierarchical core–shell structured Fe3O4@MoS2@mSiO2-folic acid (FA) (FMS-FA) nanocarrier is successfully synthesized, and the magnetic and photothermal investigations indicate that the FMS-FA not only shows strong magnetism and excellent magnetic resonance imaging (MRI) performance, but also has a good photothermal stability with a high photothermal conversion efficiency. With a pore structure, the FMS-FA exhibits a strong DOX-loading capacity, and reveals obvious pH and near infrared (NIR) laser-responsive drug release characteristics, fitting well to the Korsmeyer-Peppas model. In-vitro cellular experiments reveal that the FMS-FA nanocarrier displays low cytotoxicity, whereas the DOX-loaded Fe3O4@MoS2@mSiO2-FA-DOX (FMS-FA-DOX) nanosystem exhibits a high Hela-cell killing effect especially under irradiation with the NIR laser. Additionally, the FMS-FA-DOX could be selectively targeted to the two-dimensional (2D) uterine cancer (HeLa) cell model and the three-dimensional (3D) breast cancer (MDA-MB-231) cell microsphere model, it is efficiently internalized via folate receptor-mediated endocytosis, exhibiting dose-dependent anticancer cellular efficacy. Our synthesized FMS-FA-DOX platform enables tumor targeting, drug release control, and MRI guidance, and exerts synergistic effects of photothermal-/chemo- therapies to effectively inhibit tumor-cell growth in vitro, offering a novel strategy for tumor therapy.