Amphiphilic polypeptide P23: design, synthesis, self-assembly and its encapsulation effect on doxorubicin

Polypeptides are a new type of drug carrier materials that have attracted extensive attention owing to their favorable properties like good biocompatibility and biodegradability. In this paper, we report the design and synthesis of a tumor-targeting amphiphilic polypeptide P23 (DGRKKKKAAVALLPAVLLALLAP) consisting of a hydrophilic head and hydrophobic tail containing the amino-acid sequences DGRKKKK and AAVALLPAVLLALLAP, respectively, which can self-assemble into nanospheres in an aqueous solution and encase doxorubicin (DOX). The ability for drug release and in-vitro release kinetics of the P23@DOX composite were thoroughly studied in simulated gastric juice, tumor microenvironment, and intestinal fluid models. Cytotoxicity tests demonstrated that the toxicity levels of P23 against cells were low, but P23@DOX was more cytotoxic to 4T1 tumor cells than pristine DOX, indicating that the tumor-targeting performance of P23@DOX was good and it could be used as a drug carrier in tumor-targeting drug delivery systems.