Hydrangea-structured tumor microenvironment responsive degradable nanoplatform for hypoxic tumor multimodal imaging and therapy

Developing new strategies to alleviate tumor hypoxia and enhance the therapeutic efficacy towards solid tumors is of great significance to tumor therapy. Herein, to overcome tumor hypoxia, specifically designed aza-BODIPY photosensitizer is co-loaded with anti-cancer drug (doxorubicin, DOX) onto the hydrangea-structured MnO2 nanoparticles, and a tumor microenvironment (TME) responsive degradable nanoplatform (MDSP NP) is established. MDSP NPs (∼54 nm), with near infrared absorption (∼853 nm), can be rapidly dissociated to generate oxygen in response to TME, whereby improving tumor hypoxia, in favor of effective drugs release and enhanced chemo/photodynamic therapy. Revealed by in vivo fluorescence and photoaccoustic imaging, MDSP NPs are preferential accumulated at tumor site. Confirmed by photothermal imaging, MDSP NPs can induce hyperthermia to relieve hypoxia, promote the uptake of therapeutic nanoparticles, and further reduce the resistance and improve the therapeutic efficiency. As a result, a remarkable synergistic tumor chemo/photodynamic/photothermal therapy with hydrangea-structured TME responsive oxygen-self-generation nanoplatform is confirmed by both in vitro and in vivo studies, testifying its great potential for hypoxic tumor treatment in clinical application.