W₁₈O₄₉-mediated photodynamic therapy (PDT) and photothermal therapy (PTT) are limited by the easily oxidized property and tumor hypoxia. Here, we report the development of platelet membranes as nanocarriers to co-load W₁₈O₄₉ nanoparticles (NPs) and metformin (PM-W₁₈O₄₉-Met NPs). Platelet membranes can protect W₁₈O₄₉ from oxidation and immune evasion, and increase the accumulation of W₁₈O₄₉ in tumor sites via the passive EPR effect and active adhesion between platelets and cancer cells. The introduction of metformin (Met), a typical anti-diabetic drug, can alleviate the tumor hypoxia through reducing oxygen consumption. As a result, ROS and heat generation are both greatly increased, as revealed by ROS/hypoxia imaging in vitro, IR thermal imaging in vivo and PET imaging in vivo. PM-W₁₈O₄₉-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced tumor cell apoptosis. Therefore, our work provides a novel strategy for simultaneous enhanced PDT and PTT, which is promising in bioapplication. STATEMENTE OF SIGNIFICANCE: W₁₈O₄₉-mediated photodynamic therapy and photothermal therapy are limited by the poor delivery of nanoparticles to tumors, the easily oxidized property, and tumor hypoxia environment, which will induce tumor treatment failure. Herein, we report the development of platelet membranes as nanocarriers to co-load W₁₈O₄₉ nanoparticles and metformin (PM-W₁₈O₄₉-Met NPs). Platelet membranes can protect W₁₈O₄₉ from oxidation and immune evasion, and increase the accumulation of W₁₈O₄₉ in tumor sites via the passive EPR effect and active adhesion. Metformin can alleviate the tumor hypoxia through reducing oxygen consumption. Hence, ROS and heat generation are both greatly increased. PM-W₁₈O₄₉-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced apoptosis. Therefore, our work provides a novel strategy in bioapplication.

Junxian Tao

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