School of Pharmacy, Nantong University, No. 19 Qixiu Road, Nantong, 226001, China.
NICM Health Research Institute, Western Sydney University, Westmead, Australia.
Carbohydr Polym. 2021 Aug 1;265:118071. doi: 10.1016/j.carbpol.2021.118071. Epub 2021 Apr 16.
Spontaneous formation of protein corona on chitosan-based nano-carriers is inevitable once they enter the blood, which is considered to be an important factor that weakens the delivery efficiency and therapeutic effect of nucleic acid drugs. For this, cyclic RGDyK peptide (cRGD) modified bovine serum albumin (BSA) was designed as a corona to precoat on redox-responsive chitosan-based nano-carriers (TsR NPs) before administration. The effects of the precoating corona on the pharmaceutical properties and delivery efficiency of the nano-carriers and the therapeutic effect of model siRNA (siVEGF) were investigated. The results showed that BSA-cRGD formed steady corona around TsR NPs, which enhanced targeting ability to cancer cells and reduced serum proteins adsorption. The Bc corona improved the stability and biocompatibility of TsR NPs, increased the intracellular uptake, facilitated the lysosomal escape and maintained their redox-sensitive responsiveness, resulting in enhanced gene silencing efficiency and anti-tumor proliferation effects both in vitro and in vivo.
壳聚糖基纳米载体一旦进入血液，其表面不可避免地会自发形成蛋白质冠，这被认为是降低核酸药物递送效率和治疗效果的一个重要因素。为此，设计了环 RGDyK 肽（cRGD）修饰的牛血清白蛋白（BSA）作为冠，在给药前预先涂覆在氧化还原响应性壳聚糖基纳米载体（TsR NPs）上。研究了预涂层冠对纳米载体的药物性质和递送效率以及模型 siRNA（siVEGF）的治疗效果的影响。结果表明，BSA-cRGD 在 TsR NPs 周围形成了稳定的冠，增强了对癌细胞的靶向能力，并减少了血清蛋白的吸附。Bc 冠提高了 TsR NPs 的稳定性和生物相容性，增加了细胞内摄取，促进了溶酶体逃逸，并保持了它们的氧化还原敏感响应性，从而增强了体外和体内的基因沉默效率和抗肿瘤增殖作用。
