Engineered Red Blood Cell Membrane‐Coating Salidroside/Indocyanine Green Nanovesicles for High‐Efficiency Hypoxic Targeting Phototherapy of Triple‐Negative Breast Cancer

Abstract Triple‐negative breast cancer (TNBC) presents special biological behavior and clinicopathological characteristics and leads to a worse prognosis than other types of breast cancer. The development of an effective therapeutic method is significant to improve the survival rate of TNBC cancer patients. In this work, an engineered red blood cell membrane (RBCm)‐coating salidroside/indocyanine green nanovesicle (ARISP) is successfully prepared for hypoxic targeting phototherapy of TNBC. Salidroside in ARISP effectively ameliorates hypoxia‐induced tumorigenesis by downregulating the expression of hypoxia‐inducible factor 1α (HIF‐1α), which increases the killing effect of reactive oxygen species on tumor cells during photodynamic therapy (PDT) using the photosensitizer indocyanine green. Besides, ARISP has an anti‐LDLR modified RBCm‐coating that extends its circulation time in the blood and escapes from immune surveillance and enhances hypoxia‐targeted cellular uptake via the overexpressed LDLR receptor in hypoxic tumor sites. Moreover, guided by near‐infrared fluorescence imaging and photoacoustic imaging, ARISP can eliminate tumors via high‐efficiency phototherapy and inhibit lung and liver metastasis in TNBC models. Cytotoxicity assay of ARISP indicates the excellent biocompatibility with normal cells and tissues. This study provides fulfilling insights into the anticancer mechanism of reducing HIF‐1α for enhanced PDT and has a promising therapeutic potential for TNBC treatment.