Intracellular delivery of cytochrome C using hypoxia-responsive polypeptide micelles for efficient cancer therapy

To begin with, it is important to note that biodegradable polypeptides have been extensively applied as drug delivery carriers due to their excellent bioavailability, neglectful toxicity, good encapsulation and controlled release. Thus, a biodegradable and hypoxia-responsive polypeptide is a benefit when synthesized for the intracellular delivery of cytochrome c (CC). In its most positive context, this amphiphilic polypeptide can self-assemble into core/shell-structured micelles and encapsulate CC in their hydrophobic cores. Owing to the presence of hypoxia-responsive chemical bonds, the CC-loaded polymeric micelles (PMs) can potentially target hypoxic tissues (such as tumors) and release the proteins inside the cancer cells. For this reason, these PMs exhibit high protein loading content and efficiency and remain stable in several different kinds of cell culture media under normoxic condition. Moreover, the confocal microscopy indicates that CC-loaded PMs could be effectively uptaken by cancer cells and accelerate endo/lysosomal escape. Most importantly, the CC-loaded PMs show great killing effect to HepG2 liver cancer cells under hypoxic condition, which makes this nano-platform a promising candidate for use with efficient cancer therapy.

Keywords: Endo/lysosomal escape; Hypoxia-responsive; Polymeric micelles; Polypeptide; Protein delivery.