Multifunctional oxygen vacancy defect-rich magnetic nanoplatforms for MR imaging and enhanced chemodynamic therapy synergized with chemotherapy and photothermal therapy.

Recently, the chemodynamic therapy (CDT)-based multimodal synergistic therapy with image guiding by using properly designed nanoplatforms has reveals huge potential for efficient tumor therapy. However, the therapeutic efficiency is still limited by the insufficient intracellular H2O2 and high reductive glutathione (GSH) levels in tumor microenvironment. In this study, a multifunctional nanoplatform (DOX-CIMPT) was designed by coating mesoporous polydopamine (MPDA) on the surface of oxygen vacancy defect (OVD)-rich cerium doped iron oxide nanoparticles (CeIONCs), following with PEGylated transferrin (PEG-Tf) modification and doxorubicin (DOX) loading. The prepared DOX-CIMPT nanoplatform exhibited excellent biocompatibility, colloidal stability as well as MRI contrast agent capability, and the MPDA shell permitted remarkable drug loading and GSH depletion capabilities due to the high surface area, abundant chemical function groups and α, β-unsaturated carbonyl structures. The released DOX from DOX-CIMPT can promote the formation of superoxide radicals (O2•-), while inducing chemotherapy (CT) effect. In addition, the DOX-CIMPT exhibited enhanced multienzyme-like capabilities of superoxide dismutase (SOD) and peroxidase (POD) for the relay reactions of O2•-→ H2O2→ •OH due to the OVD-rich CeIONC cores. Therefore, proper TME modulation and improved •OH generation was achieved by the developed DOX-CIMPT nanoplatform. Moreover, the local heat from photothermal therapy (PTT) process could trigger drug release and further enhance the generation of •OH. In addition, the synergistic combination of CDT/CT/PTT by DOX-CIMPT exhibited significantly enhanced anticancer effect in in vitro cell test. Thus, we believe that the developed DOX-CIMPT nanoplatform will provide a novel paradigm for efficient MRI guided synergistic tumor therapy.