Self-amplifying violet phosphorus-manganese nanocatalysts disrupt redox homeostasis and potentiate antitumor immunity via NIR-II phototherapy.

Abstract

Nanocatalytic therapy holds great promise in tumor treatment. However, its antitumor efficacy is substantially hindered by limitations of the tumor microenvironment (TME), including substrate the type and concentration of substrates, pH value, antioxidant stress defense mechanisms, and immunosuppressive milieu. This study presents a nanoplatform composed of manganese-in-situ-mineralized violet phosphorus nanosheets (VPNSs), abbreviated as MVPs. This platform enables both the disruption of redox homeostasis and activation of antitumor immunity through regulation by the TME and near-infrared II region (NIR-II) light stimulation. Within MVPs, VPNSs not only function as electron donors to sustain the concentration of active Mn²⁺ in the TME and amplify the Mn²⁺-mediated self-enhanced chemodynamic therapy (CDT), but also serve as NIR-II photocatalysts. The photocatalytic properties synergistically elevate the level of reactive oxygen species (ROS) at the tumor site, thereby disrupting the redox homeostasis of tumor cells. Furthermore, the NIR-II photothermal characteristic of MVPs enhances the Mn²⁺-mediated activation of the stimulator of interferon genes (STING) pathway, endowing MVPs with antitumor immune activation capability. MVPs demonstrate excellent tumor therapeutic performance and biocompatibility in female tumor-bearing mice with a tumor inhibition rate of 85.24 %, achieving "catalysis-photothermal-immunity" synergistic antitumor activity.