Keratin-Poly(2-methacryloxyethyl phosphatidylcholine) Conjugate Based Micelles as Tumor Microenvironment-Responsive Drug Delivery System with Long Blood Circulation.

Drug-loaded micelles with long circulation time in blood and stimuli-responsiveness under tumor microenvironment can signi fi cantly enhance the therapeutic e ffi cacy. In this report, human hair keratin was extracted with a reduction method and then conjugated with zwitterionic poly(2-methacryloxyethyl phosphatidylcholine, MPC) via thiol chain transfer polymerization(Thiol CTP). Subsequently, keratin-polyMPC conjugates (KPC) were prepared into micelles and loaded with doxorubicin (DOX) by self-assembly. These micelles exhibited pH, glutathione (GSH), and enzyme triple-responsiveness as well as charge reversibility under the tumor microenvironment. In addition, these micelles showed high toxicity against A549 cells while low toxicity to normal cells. In vivo anticancer efficacy results revealed that these micelles performed better therapeutic efficiency than free DOX. Furthermore, these carriers exhibited the prolonged circulation time, good stability, and no hemolysis in blood. Based on the results, these drug delivery systems of micelles were proper candidates as drug carriers.