Dual-stimuli sensitive keratin graft PHPMA as physiological trigger responsive drug carriers

Keratin graft poly(N-(2-hydroxypropyl)methacrylamide) (K-g-PHPMA) copolymers were synthesized and characterized. On account of the thiol groups of keratin and the amphiphilicity of the graft copolymers, micelles with cleavable cross-links on a keratin core were fabricated in water. The K-g-PHPMA micelles can efficiently encapsulate doxorubicin (DOX) and can be used as a drug carrier. The DOX content in the micelles increases with the keratin content of the graft copolymers. The release of the encapsulated DOX in the micelles is sensitive to the physiological environment. Redox trigger glutathione (GSH), especially at the intracellular level, and trypsin can effectively trigger the release of the encapsulated DOX. In vitro cellular uptake experiments indicate that the DOX released from the DOX-loaded K-g-PHPMA micelles can be efficiently internalized into cells. Under higher GSH condition, the DOX shows a much faster release into the nucleus of the cells. The K-g-PHPMA copolymers have promising applications as drug carriers for enhanced intracellular drug delivery in cancer therapy.