Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Guangdong Medical University, Dongguan 523808, China.
Mater Sci Eng C Mater Biol Appl. 2017 Apr 1;73:189-197. doi: 10.1016/j.msec.2016.12.067. Epub 2016 Dec 15.
Smart drug carriers are the current need of the hour in controlled drug delivery applications. In this work, pH and redox dual responsive keratin based drug-loaded nanoparticles (KDNPs) were fabricated through two-step strategies. Keratin nanoparticles were first prepared by desolvation method and chemical crosslinking, followed by electrostatic adsorbing doxorubicin (DOX) to afford drug loaded keratin nanoparticles (KDNPs). The size, size distribution, and morphology of the KDNPs were characterized with dynamic light scattering (DLS) and Scan electronic microscope (SEM). Drug delivery profiles showed that KDNPs exhibited pH and glutathione (GSH) dual-responsive characters. Under tumor tissue/cell microenvironments (more acidic and high GSH level), KDNPs tended to accumulate at the tumor region through a potential enhanced permeability and retention (EPR) effect and perform surface negative-to-positive charge conversion. Hemolysis assay indicated that KDNPs had good blood compatibility. Cellular uptake assay demonstrated that KDNPs could be internalized by A 549 cells through endocytosis. Intriguingly, KDNPs were capable of promoting nitric oxide (NO) release from endogenous donor of S-nitrosoglutathione in the presence of GSH. All of these results demonstrated that keratin based drug carriers had potential for drug/NO delivery and cancer therapy in clinical medicine.
智能药物载体是当前控制药物递送应用的迫切需求。在这项工作中，通过两步策略制备了 pH 和氧化还原双重响应角蛋白载药纳米颗粒（KDNPs）。首先通过去溶剂化法和化学交联制备角蛋白纳米颗粒，然后通过静电吸附阿霉素（DOX）得到载药角蛋白纳米颗粒（KDNPs）。通过动态光散射（DLS）和扫描电子显微镜（SEM）对 KDNPs 的粒径、粒径分布和形态进行了表征。药物释放曲线表明，KDNPs 表现出 pH 和谷胱甘肽（GSH）双重响应特性。在肿瘤组织/细胞微环境（更低的 pH 值和更高的 GSH 水平）下，KDNPs 通过潜在的增强渗透和保留（EPR）效应在肿瘤区域聚集，并发生表面负电荷到正电荷的转换。溶血试验表明 KDNPs 具有良好的血液相容性。细胞摄取试验表明，KDNPs 可以通过内吞作用被 A549 细胞内化。有趣的是，在 GSH 的存在下，KDNPs 能够促进来自 S-亚硝基谷胱甘肽内源性供体的一氧化氮（NO）释放。所有这些结果表明，角蛋白载药载体在临床医学中具有药物/NO 递药和癌症治疗的潜力。
