National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China.
Carbohydr Polym. 2017 Nov 1;175:159-169. doi: 10.1016/j.carbpol.2017.07.078. Epub 2017 Jul 29.
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.
本文制备了一种新型的双重响应纳米凝胶，该纳米凝胶由角蛋白和海藻酸钠通过简单的交联方法制备而成。角蛋白提供了交联结构和生物响应能力，海藻酸钠改善了纳米凝胶的性质，包括粒径、稳定性和载药能力。所得角蛋白-海藻酸钠纳米凝胶（KSA-NGs）可用作盐酸阿霉素（DOX）的有前途的载体，具有超高的载药率（52.9%（w/w））和对 GSH 和胰蛋白酶的双重刺激响应行为。细胞摄取结果表明，DOX 负载的 KSA-NGs（DOX@KSA-NGs）在体外能够有效地被 4T1 和 B16 细胞内化，并且在细胞内 GSH 和胰蛋白酶水平下，DOX 能够快速释放到细胞内。体外细胞毒性结果进一步表明，DOX@KSA-NGs 对肿瘤细胞的抑制作用与 DOX 相当。体内实验表明，与游离药物相比，DOX@KSA-NGs 具有更好的抗肿瘤效果和更低的副作用。这些生物响应性 KSA-NGs 有望作为癌症治疗的纳米载体。
