Saponin-mediated cell membrane interference nanomedicine potentiates tumor chemo-immunotherapy via perforin-granzyme-like mechanism

Pore formation can facilitate the release of various intracellular substances upon cell death, which is of critical benefit for tumor immunotherapy by immunogenic cell death (ICD). Given the effective endogenous antigen release is of primary importance for ICD-eliciting immunogenicity, other than by enhancing the cytotoxicity of ICD, we designed an immunogenic induction strategy via pore formation based on saponin, a composite medium of the membrane-disrupting agent. In this study, saponin/polyphenol (ZS-TA) at proper concentrations can directly cause membrane perforation by removal of cholesterol from the membrane, thereby lead to the release of intracellular substances. Simultaneously, in situ nano-antigens (nano-Ag) would be formed through the mechanism of protein-polyphenol interaction and the nano-Ag would be served as reservoirs of antigen to trigger long-term immune effects. Meanwhile, this membrane perforation could also enhance the uptake of chemotherapeutic drugs, which could be served as a general approach for drug delivery. Therefore, this work insights for the design of enhanced drug delivery system and in situ vaccines to sensitize tumor chemo-immunotherapy.