Abstract
Keratin-based drug carriers have attracted great interest due to their intrinsic biocompatibility and tumor micro-environmental responsiveness. In the study, keratin was first extracted from human hair with reduction method. The reduced keratin was successively conjugated with poly(ethylene glycol) (PEG) via thiol Michael addition reaction and iodoacetic acid (IAA) via substitution reaction to impart both physical stability and acidity responsiveness. Subsequently, the conjugated keratin was fabricated into micelles and loaded with doxorubicin (DOX) by self-assembly. The micelles exhibited pH, glutathione (GSH) and enzyme (trypsin) triple-responsiveness as well as charge reversibility under the simulated tumor microenvironment. These drug-loaded micelles exhibited high toxicity against A549 cells with low side effect on normal cells. Furthermore, anticancer efficacy in vivo revealed DOX-loaded micelles presented higher therapeutic efficiency than free DOX. Moreover, these micelles were stable under physiological conditions, and could be internalized through endocytosis without hemolysis. Based on the results, the drug-loaded micelles were satisfactory candidates for drug carriers.
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