Bio-responsive alginate-keratin composite nanogels with enhanced drug loading efficiency for cancer therapy

•We synthesized functional nanogels with high drug loading capacity.•These nanogels have around 80nm and enzyme-/GSH- responsive property.•DOX loaded nanogels showed excellent inhibitory effects on tumor cells in vitro.•DOX loaded nanogels had a better anti-tumor effect and lower side effects in vivo. This article presents a novel dual-stimuli responsive nanogel prepared from human hair keratin and alginate through simple crosslinking method. Keratin offer the crosslinking structure and bio-responsive ability and alginate ameliorated properties of nanogels including particle size, stability and drug loading capacity. The resultant keratin-alginate nanogels (KSA-NGs) could function as promising vectors for doxorubicin hydrochloride (DOX) with a super-high drug-loading rate of 52.9% (w/w) and dual-stimuli responsive behavior to GSH and trypsin. Cellular uptake results indicated DOX loaded KSA-NGs (DOX@KSA-NGs) are efficiently internalized in 4T1 and B16 cells in vitro, with a fast DOX release into cells under intracellular GSH and trypsin levels. In vitro cytotoxicity results further manifested that DOX@KSA-NGs behaved equivalent inhibition effects on tumor cells to DOX. In vivo experiments showed that DOX@KSA-NGs had a better anti-tumor effect and lower side effects compared to free drugs. These bio-responsive KSA-NGs have potential applications as nanocarriers for cancer therapy.