An ATF(24) peptide-functionalized beta-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment

Objective: In this study, we aimed to develop an amino terminal fragment (ATF) peptide-targeted liposome carrying beta-elemene (ATF(24)-PEG-Lipo-beta-E) for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin (DDP) for bladder cancer treatment. Methods: The liposomes were prepared by ethanol injection and high-pressure microjet homogenization. The liposomes were characterized, and the drug content, entrapment efficiency, and in vitro release were studied. The targeting efficiency was investigated using con focal microscopy, ultra-fast liquid chromatography, and an onhotopic bladder cancer model. The effects of ATF(24)-PEG-Lipo-beta-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, and cell apoptosis and cell cycle analyses. The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model. Results: ATF(24)-PEG-Lipo-beta-E had small and uniform sizes (similar to 79 nm), high drug loading capacity (similar to 5.29 mg/mL), high entrapment efficiency (98.37 +/- 0.95%), and exhibited sustained drug release behavior. ATF(24) -PEG-Lipo-beta-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol (PEG)ylated beta-elemene liposomes (PEG -Lipo-beta-E). DDP, combined with AIF(24) -PEG-Lipo-beta-E, exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase, and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways. Furthermore, the in vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors, using the combined strategy. Conclusions: The present study provided an effective strategy for the targeted delivery of beta elemene (beta-E) to bladder cancer, and a combined strategy for bladder cancer treatment.