Self-generation of oxygen and simultaneously enhancing photodynamic therapy and MRI effect: An intelligent nanoplatform to conquer tumor hypoxia for enhanced phototherapy

Abstract The tumor microenvironment (TME) is the internal environment where tumor cells grow and develop. Constructing TME-activatable, specific imaging and treatment system is highly desired for accurate cancer diagnosis and therapy. Herein, by utilizing the degrading ability of honeycomb MnO2 in the TME, a tumor-targeted and O2-evolving photothermal/photodynamic therapeutic nanoplatform with dual-modal imaging capability was designed and fabricated. In the structure, self-assembled MnO2 was regarded as a carrier for cargo loading and O2 production, and subsequently the CuS nanoparticles (NPs) and indocyanine green (ICG) molecules with ultra- high loading characteristics (CuS NPs could be loaded up to nearly 66.8% and ICG molecules could be loaded up to 80.22%) were loaded and further wrapped in hyaluronic acid (HA), endowing the system with the capability for specific interaction with CD44 over-expressed on tumor cells. Upon irradiation with 808 nm laser, the photothermal therapy (PTT) effects of the CuS NPs and ICG molecules would be triggered with satisfactory photostability. The degradation of the carrier could generate O2, thus solving the problem of hypoxia in the TME. Simultaneously, the released ICG molecules could also exert strong photodynamic therapy (PDT) effects when activated by the same light. Indeed, PTT and PDT are two kinds of light-mediated treatment. Moreover, the recovered fluorescence of the ICG molecules and the released Mn2+ resulted in excellent fluorescent imaging and T1-weighted MR imaging. An imaging directed synergistic phototherapy has thereby been realized.