Platelet-mimicking nanoparticles co-loaded with W 18 O 49 and metformin alleviate tumor hypoxia for enhanced photodynamic therapy and photothermal therapy.

W18 O49 -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 W18 O49 nanoparticles (NPs) and metformin (PM-W18 O49 -Met NPs). Platelet membranes can protect W18 O49 from oxidation and immune evasion, and increase the accumulation of W18 O49 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-W18 O49 -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: W18 O49 -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 W18 O49 nanoparticles and metformin (PM-W18 O49 -Met NPs). Platelet membranes can protect W18 O49 from oxidation and immune evasion, and increase the accumulation of W18 O49 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-W18 O49 -Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced apoptosis. Therefore, our work provides a novel strategy in bioapplication.