pH-Activated surface charge-reversal double-crosslinked hyaluronic acid nanogels with feather keratin as multifunctional crosslinker for tumor-targeting DOX delivery

Abstract Feather keratin (FK) was used as a multifunctional crosslinker for the fabrication of both pH responsive ionically and reduction responsive covalently crosslinked hyaluronic acid (HA) nanogels, as pH-activated surface charge-reversal double-crosslinked protein/polysaccharide complex nanocarriers for the tumor-targeting DOX delivery. The effect of the preparation condition on the diameter and the drug-loading capacity of the resultant drug delivery systems (DDSs) were investigated in detail. The in vitro controlled release profiles indicated the pH/reduction dual-responsive sustained release of DOX from the proposed double-crosslinked DOX@C-FK/HA nanogels. The in vitro experiments demonstrated that the DOX@C-FK/HA nanogels could be internalized into the HCT 116 cells via a CD44-receptor-mediated endocytosis pathway, exhibiting an enhanced anti-tumor efficacy than the free DOX.