Keratin-based drug-protein conjugate with acid-labile and reduction-cleavable linkages in series for tumor intracellular DOX delivery

Abstract

Abstract PK-SS-Hy-D drug-protein prodrug was obtained by conjugating doxorubicin (DOX) onto the PEGylated keratin (PK) with both bioreducible disulfide linkage and acid-cleavable hydrazone bond in a series connection mode. The controlled release profiles demonstrated the pH and reduction dual-responsive triggered release of DOX from the proposed drug-protein conjugate nanoparticles, with a low premature drug leakage of 5.5% in the simulated physiological medium. The in vitro experiments indicated that the proposed prodrug nanoparticles could delivery DOX into the cell nuclei, with an enhanced anti-tumor efficacy. It is expected as a potential candidate for future tumor chemotherapy with minimized toxic side effect.