纳米医学
小干扰RNA
胶束
RNA干扰
材料科学
药物输送
基因沉默
药品
化学
纳米技术
药理学
生物物理学
转染
纳米颗粒
核糖核酸
医学
生物
生物化学
物理化学
基因
水溶液
作者
Tong Jiang,Yonghan Qiao,Weimin Ruan,Dongya Zhang,Qingshan Yang,Xiaogang Wang,Qunzhi Chen,Fengping Zhu,Jinlong Yin,Yan Zou,Qian Ran,Meng Zheng,Bingyang Shi
标识
DOI:10.1002/adma.202104779
摘要
Nanoparticle-based small interfering RNA (siRNA) therapy shows great promise for glioblastoma (GBM). However, charge associated toxicity and limited blood-brain-barrier (BBB) penetration remain significant challenges for siRNA delivery for GBM therapy. Herein, novel cation-free siRNA micelles, prepared by the self-assembly of siRNA-disulfide-poly(N-isopropylacrylamide) (siRNA-SS-PNIPAM) diblock copolymers, are prepared. The siRNA micelles not only display enhanced blood circulation time, superior cell take-up, and effective at-site siRNA release, but also achieve potent BBB penetration. Moreover, due to being non-cationic, these siRNA micelles exert no charge-associated toxicity. Notably, these desirable properties of this novel RNA interfering (RNAi) nanomedicine result in outstanding growth inhibition of orthotopic U87MG xenografts without causing adverse effects, achieving remarkably improved survival benefits. Moreover, as a novel type of polymeric micelle, the siRNA micelle displays effective drug loading ability. When utilizing temozolomide (TMZ) as a model loading drug, the siRNA micelle realizes effective synergistic therapy effect via targeting the key gene (signal transducers and activators of transcription 3, STAT3) in TMZ drug resistant pathways. The authors' results show that this siRNA micelle nanoparticle can serve as a robust and versatile drug codelivery platform, and RNAi nanomedicine and for effective GBM treatment.
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