Platelet membrane fusion liposome loaded with type I AIE photosensitizer to induce chemoresistance cancer pyroptosis and immunogenic cell death for enhancing cancer immunotherapy

Abstract

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 liposome 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.