School of Life Sciences, Jilin University, Changchun, China.
School of Life Sciences, Jilin University, Changchun, China; Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, OH, USA.
Nanomedicine. 2019 Aug;20:102017. doi: 10.1016/j.nano.2019.102017. Epub 2019 May 22.
Systemic delivery of siRNA to target tissues is difficult to achieve owing to its limited cellular uptake and poor serum stability. Herein, polymeric nanoparticles were developed for systemic administration of siRNA to inflamed tissues. The polymeric nanoparticles were composed of PK3 as a pH-sensitive polymer, folate-polyethyleneglycol-poly(lactide-co-glycolide) as a targeting ligand, and a DOTAP/siRNA core. The polymeric nanoparticles had a mean particle size of 142.6 ± 0.61 nm and a zeta potential of 3.6 ± 0.43 mV. In vitro studies indicated pH-dependent siRNA release from polymeric nanoparticles, with accelerated release at pH 5.0. Cellular uptake was efficient and gene silencing was confirmed by Western blot. In vivo, polymeric nanoparticles were shown to have inflammation-targeting activity and potent therapeutic effects in an adjuvant-induced arthritis rat model. These results suggest that pH-sensitive and folate receptor-targeted nanoparticles are a promising drug carrier for siRNA delivery for rheumatoid arthritis.
由于其有限的细胞摄取和较差的血清稳定性，很难将 siRNA 递送到靶组织。本文开发了用于将 siRNA 递送到炎症组织的聚合物纳米粒。聚合物纳米粒由 PK3 作为 pH 敏感聚合物、叶酸-聚乙二醇-聚（乳酸-共-乙醇酸）作为靶向配体和 DOTAP/siRNA 核组成。聚合物纳米粒的平均粒径为 142.6±0.61nm，zeta 电位为 3.6±0.43mV。体外研究表明聚合物纳米粒具有 pH 依赖性 siRNA 释放特性，在 pH 5.0 时释放加速。细胞摄取效率高，通过 Western blot 证实了基因沉默。在体内，聚合物纳米粒在佐剂诱导的关节炎大鼠模型中表现出炎症靶向活性和强大的治疗效果。这些结果表明，pH 敏感和叶酸受体靶向纳米粒是一种有前途的类风湿关节炎 siRNA 递送药物载体。
