Short and simple peptide-based pH-sensitive hydrogel for antitumor drug delivery

Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for drug delivery. In this study, we developed a novel and injectable drug delivery platform for the antitumor drug doxorubicin (DOX) using a pH-responsive ionic-complementary octapeptide FOE. This octapeptide could self-assemble into stable hydrogel under neutral conditions, while disassemble under the tumor microenvironment. Especially, at pH 5.8, its micromorphology displayed a transition from nanofibers to nanospheres with the change of secondary structure, which enhanced cellular uptake of DOX. In addition, FOE hydrogel serves as a smart drug reservoir by localized injection to achieve sustained drug release and improve antitumor efficacy. This octapeptide opens up new avenues for promoting the clinical translation of anticancer drugs on account of excellent injectable properties and economic benefits of simple and short sequence. [Display omitted] We developed a short and simple pH-responsive ionic-complementary octapeptide FOE (FOFOFRFE), which could self-assemble into stable hydrogel at pH 7.4 due to non-covalent interactions dominated by hydrophobic interactions, as an injectable drug delivery carrier for the antitumor drug doxorubicin (DOX). After peritumoral administration, the octapeptide hydrogel disassembled under acidic microenvironment (pH 5.8), accompanied by the change of microstructure from fiber networks to nanospheres, which contributed to the achievement of controlled drug delivery and enhanced drug uptake by tumor cells.