Tumor hypoxia relief overcomes multidrug resistance and immune inhibition for self-enhanced photodynamic therapy

As the self-regulation of tumors in the tumor microenvironment (TME), the hypoxia becomes the limitation again in the last period of oxygen-rich inducing enhanced photodynamic therapy (PDT). In this study, a promising TME-triggered oxygen nanogenerator for self-enhanced PDT primed antitumor immunotherapy was designed via simple and green chemistry methods. Indocyanine green (ICG), as a multi-role photosensitizer, was applied in photothermal therapy (PTT), PDT and diagnostic imaging. Given this, we utilized the heat generated by the ICG and branched gold nanoshells to promote the catalysis of hydrogen peroxide in the TME, which synchronized the oxygen generation and enhanced PDT (called self-enhanced PDT). Furthermore, the relief of tumor hypoxia broke the chemoresistance and promoted the polarization of tumor-associated macrophages from M2 to M1 type, which heightened the efficacy of chemotherapy and immunotherapy. Overall, this work has addressed a long-term issue for the limitation of PDT resulting from hypoxia and provided a close connection among the diversified therapeutic modalities.