Anticancer Properties of Lipidated Peptide Drug Supramolecular Self-Assemblies with Enhanced Stability

Molecular modification and self-assembly are clinically proved successful strategies in drug design to enhance the treatment efficiency. Herein, the lipidation method is used to modify the anticancer tripeptides tyoservaltide (YSV) into lipidated YSV, C₁₆-EEYSV-NH₂, and C₁₆-KKYSV-NH₂. We found the lipidated YSV performed better aggregation property from the critical aggregation concentration (CAC) measurements, transmission electron microscope (TEM) and atomic force microscope (AFM) observation. The cytotoxicity experiments showed that the lipidated YSV had better anticancer efficiency due to their excellent self-assembly. Meantime, the lipidated YSV shows superior biostability and cells internalization which can be proved by high performance liquid chromatography (HPLC), inverted fluorescence microscope, and flow cytometry (FCM). For in vivo experiments, the results also showed that lipidated YSV have better performance, and the final histology analysis shows low toxicity to the body organs. Considering the advantages of lipidated YSV, we hope that our study would demonstrate a powerful strategy to improve the application of peptide drugs.