SRT3025-loaded cell membrane hybrid liposomes enhanced anti-carcinoma activity of Oxaliplatin via inhibiting pyruvate kinase M2 and fatty acid synthase

Background Bladder cancer is one of the most common malignancies of the urinary system, and despite significant advances in diagnosis and treatment, oxaliplatin resistance remains a major clinical challenge. Thus, developing a novel delivery system is required to overcome oxaliplatin resistance and improve patient outcomes. Methods Bladder cancer cell lines, T24 and 5637, were cultured in McCoy’s 5A and RPMI 1640 medium, respectively. The phospholipids and cell membranes were used to formulate the hybrid liposomes. Cell Counting Kit-8 assay was used to determine the cell viability and proliferation. Cell death and apoptosis were quantified by trypan blue, calcein-AM/PI double staining, and Annexin V-APC/PI apoptosis assay. Western blot analysis was used to determine the proteins level. Results The present study demon s trated that SRT3025-loaded cell membrane hybrid liposomes (3025@ML) enhance the chemosensitivity to oxaliplatin (OXA). 3025@ML monotherapy as well as the combination therapy, 3025@ML plus OXA significantly enhanced the anti-carcinoma activity of OXA. In mechanistic studies, 3025@ML inhibited the PI3K/AKT/mTOR signaling pathway and reduced the expression of key metabolic regulators PKM2 and FASN. Furthermore, this study demonstrated that targeting lipid metabolism and inhibiting FASN can effectively overcome oxaliplatin resistance. Conclusion The study demonstrated that SRT3025-loaded cell membrane hybrid liposomes significantly enhance the anti-tumor activity of OXA. This novel drug delivery system inhibits key metabolic pathways, increasing DNA damage and tumor cell apoptosis. The results suggest that 3025@ML is a promising therapeutic strategy for overcoming oxaliplatin resistance and improving cancer treatment outcomes.