Engineered Red Blood Cell Biomimetic Nanovesicle with Oxygen Self-Supply for Near-Infrared-II Fluorescence-Guided Synergetic Chemo-Photodynamic Therapy against Hypoxic Tumors.

The low bioavailability of photosensitizers (PSs) and the hypoxia nature of tumors often limit the efficacy of current photodynamic therapy (PDT). Therefore, improving the utilization of three essential components (PS, light, and O2) in tumors will enhance PDT efficacy substantially. Herein, we have developed a red blood cell (RBC) biomimetic theranostic nanovesicle (named SPN-Hb@RBCM) with improved photostability, accumulation of PSs, and oxygen self-supply ability to enhance PDT efficacy upon near-infrared (NIR) laser irradiation. Such a biomimetic nanovesicle was prepared by a red blood cell membrane (RBCM)-camouflaged hemoglobin (Hb)-linked semiconducting polymer nanoparticle (SPN-Hb). The RBCM coating enables the long-term circulation of SPN-Hb due to the membrane-mediated immune evasion, allowing for more effective PS accumulation in tumors. Under 808 nm laser irradiation, the photostable SPN can serve as both a photodynamic and a second-near-infrared-window (NIR-II) fluorescence imaging agent; meanwhile, the conjugated Hb can be used as an oxygen carrier to relieve tumor hypoxia for enhancing PDT efficacy. In addition, Hb can also react with the tumor microenvironment overproduced H2O2 to generate cytotoxic hydroxyl radicals (•OHs) for chemodynamic therapy (CDT), which further achieve synergistic effects for PDT. Thus, this study proposed a promising biomimetic theranostic nanoagent for enhancing tumor oxygenation and NIR-II fluorescence-guided synergetic CDT/PDT against hypoxic tumors.