Platelet Membrane Fusion Liposome Loaded with Type I AIE Photosensitizer to Induce Chemoresistance Cancer Pyroptosis and Immunogenic Cell Death for Enhancing Cancer Immunotherapy
Chemical Engineering Journal(2023)
摘要
Cancer cells often develop resistance to chemotherapy induced apoptosis, and targeting non-apoptosis-related pathways is a potential anti-drug resistant tumor strategy. Here, we designed a platelet membrane fusion lipo-some nanovesicle system (named TFL) loaded with type I aggregation induced-emission (AIE) photosensitizer (TBP-2), which is used to promote the pyroptosis and immunogenic cell death (ICD) of chemoresistance breast cancer cells. Because of the highly expressed P-selectin protein in platelets, TFL can target the highly expressed CD44 receptor in chemoresistance breast cancer cells and deliver TBP-2 molecules to these cells. Under the irradiation of external light sources, TBP-2 achieves type-I photodynamic therapy (PDT), generating a large number of hydroxyl free radicals, inducing pyroptosis and ICD of chemoresistance cancer cells, promoting DC cell maturation and T cell infiltration. In vivo animal experiments have shown that the TFL system can promote T cell immunity, slow down distal chemoresistance tumor growth, achieve immune memory effect, and inhibit chemoresistance tumor rechallenge. Compared with high-dose chemotherapy, TFL + L has better immune stimulation and therapeutic effect on drug-resistant breast cancer. This system may become an adjuvant therapy for clinical chemotherapy in the future, further enhancing the immune response and therapy effect of drug-resistant tumors.
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关键词
Chemoresistance breast cancer,Platelet membrane fusion liposome,Type-I PDT,Pyroptosis,Cancer immunotherapy
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