In this work, a tumor microenvironment (TME)-responsive biodegradable MnSiO3@Fe3O4 nanoplatform for dual-mode magnetic resonance imaging (MRI)-guided combinatorial cancer therapy was constructed. Fe3O4 nanoparticles decorated on the surface of MnSiO3 could effectively obstruct the pores of MnSiO3 and reduce the leakage of anticancer drugs under physiological conditions. The structure of the nanoplatform was broken under the weakly acidic and high-concentration glutathione conditions in the TME, resulting in the separation of the Fe3O4 nanoparticles from the nanoplatform and rapid drug release. In addition, the exfoliated Fe3O4 and released Mn2+ can help reduce the interference between their T1 and T2 contrast abilities, resulting in dual-mode MRI contrast enhancement. Furthermore, during the exfoliation process of the Fe3O4 nanocrystals, the catalytic activity of the Fe3O4 nanocrystals toward a Fenton-like reaction within cancer cells could be improved because of the increase in specific surface area, which led to the generation of highly toxic hydroxyl radicals and induced HeLa cell apoptosis. The nanoplatform also displayed excellent T1-T2 dual-mode MRI contrast enhancement and anticancer activity in vivo with reduced systemic toxicity. Thus, this multifunctional nanoplatform could be a potential nanotheranostic for dual-mode MRI-guided combinatorial cancer therapy.
Keywords: Combinatorial therapy; Degradable; Magnetic resonance imaging; Microenvironment-responsive; Nanotheranostics.
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