Engineering PD-L1 targeted liposomal canagliflozin achieves multimodal synergistic cancer therapy

作者：Simeng Wang, Mengjun Sui, Quan Chen, Jiahua Guo, Huini Yang, Ye Zhou, Meiju Ji, Yangyang Cheng, Peng Hou · 发表于：Chemical Engineering Journal · 年份：2024 · DOI：10.1016/j.cej.2024.155074 · 被引用次数：9 · 研究领域：Phagocytosis and Immune Regulation、Cancer Immunotherapy and Biomarkers、Nanoparticle-Based Drug Delivery

PD-L1 based targeting delivery of canagliflozin enables the multifaceted anti-tumor treatment. • Canagliflozin inhibits cancer progression through co-suppressing of MAPK/ERK and PI3K/AKT signaling pathways. • Canagliflozin enhances the tumor immunotherapeutic efficacy by PD-L1 degradation. • Canagliflozin sensitizes to radiotherapy by decreasing DNA damage repair-related proteins. • PD-L1 targeted liposomal canagliflozin empowers the multimodal synergistic cancer therapy. Immunotherapy-involved combination cancer therapy heralds an unstoppable revolution in clinical practice. However, designing a streamlined approach to integrate immunotherapy with other therapies remains a formidable challenge. Canagliflozin, a clinical drug for type II diabetes, has gained growing interest in cancer therapy, albeit its precise mechanism remains largely elusive. Here, we delve into the multifaceted antitumor mechanisms of canagliflozin, including co-suppression of MAPK/ERK and PI3K/AKT signaling pathways, induction of PD-L1 degradation via ubiquitination and sensitization to X-ray irradiation via downregulation of DNA damage repair-related molecules, thereby offering opportunities for synergistic cancer treatment. For this purpose, we designed a universal nanoliposome coated with a PD-L1-targeting peptide to efficiently deliver canagliflozin in vivo . This simple fabricated nanodrug exhibited specific tumor-targeting ability and excellent biosafety. In vivo anti-cancer efficacy evaluation re...