Glutathione-responsive polypeptide nanogel encapsulates Shikonin for breast cancer therapy.

Exploiting the unique physiological and biochemical characteristics of the tumor microenvironment, the development of a polypeptide nanogel capable of responding to these specific properties holds great promise as an effective antitumor strategy. In this study, we synthesized a glutathione-responsive (GSH-responsive) methylated poly (ethylene glycol)-poly (phenylalanine)-poly (cystine) block copolymer (mPPC) through one-step ring-opening polymerization. Shikonin (SHK) was encapsulated within nanogel, designated as mPPC/SHK. The biocompatible and safe nature of mPPC facilitated its accumulation at the tumor site through enhanced permeability and retention effect, leading to efficient release of SHK upon stimulation by high concentrations of GSH. As anticipated, the group of mPPC/SHK displayed enhanced efficacy against tumors, resulting in a tumor inhibition rate of 69.97 % in the 4T1 breast cancer model. Overall, this GSH-responsive polypeptide nanogel encapsulating SHK has tremendous potential as a promising biomedical agent for effective tumor nanotherapy.