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. 1.The SHK was encapsulated in a polypeptide nanogel known as mPPC, resulting in the formation of mPPC/SHK.2.Through the enhanced permeability and retention effect, mPPC/SHK efficiently accumulated at the tumor site and effectively penetrated into the tumor tissue from blood vessels.3.Upon internalization by tumor cells, mPPC/SHK underwent degradation triggered by high intracellular concentration of GSH, leading to the release of SHK for effective cell killing. [Display omitted] •In the 4T1 mouse model, mPPC-Cy5 accumulated at the tumor site and remained fluorescent even after 168 h.•In the 4T1 mouse model, mPPC/SHK exhibited superior therapeutic efficacy.•mPPC demonstrated excellent biocompatibility.