Abstract 4481: Targeting Xkr8 via nanoparticles-mediated codelivery of siRNA and chemotherapy drugs for cancer immunochemotherapy

Abstract Activation of scramblases is one of the mechanisms that regulate the exposure of phosphatidylserine to the cell surface, a process that plays an important role in tumor immunosuppression. Here we show that chemotherapeutic agents induce overexpression of Xkr8, a scramblase activated during apoptosis, at the transcriptional level in cancer cells, both in vitro and in vivo. Given this finding, we developed a nanocarrier for co-delivery of Xkr8 siRNA and the FuOXP pro-drug to tumors. Intravenous injection of our nanocarrier led to significant inhibition of tumor growth in colon and pancreatic cancer models along with increased antitumor immune response. Targeting Xkr8 in combination with chemotherapy may represent a novel strategy for the treatment of various types of cancers. Citation Format: Yuang Chen. Targeting Xkr8 via nanoparticles-mediated codelivery of siRNA and chemotherapy drugs for cancer immunochemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4481.