Platelet membrane biomimetic nanoparticle-targeted delivery of TGF-β1 siRNA attenuates renal inflammation and fibrosis

血小板膜仿生纳米颗粒靶向递送 TGF-β1 siRNA 可减轻肾脏炎症和纤维化

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作者:Shengnan Fei, Yidan Ma, Bing Zhou, Xu Chen, Yuan Zhang, Kun Yue, Qingxin Li, Yuanyuan Gui, Tianya Xiang, Jianhang Liu, Bin Yang, Lei Wang, Xinzhong Huang

Abstract

The progression of renal fibrosis to end-stage renal disease (ESRD) is significantly influenced by transforming growth factor-beta (TGF-beta) signal pathway. This study aimed to develop nanoparticles (PMVs@PLGA complexes) with platelet membrane camouflage, which can transport interfering RNA to target and regulate the TGF-β1 pathway in damaged renal tissues. The aim is to reduce the severity of acute kidney injury and to reduce fibrosis in chronic kidney disease. Hence, we formulated PMVs@TGF-β1-siRNA NP complexes and employed them for both in vitro and in vivo therapy. From the experimental findings we know that the PMVs@siRNA NPs could effectively target the kidneys in unilateral ureteral obstruction (UUO) mice and ischemia/reperfusion injury (I/R) mice. In animal models of treatment, PMVs@siRNA NP complexes effectively decreased the expression of TGF-β1 and mitigated inflammation and fibrosis in the kidneys by blocking the TGF-β1/Smad3 pathway. Therefore, these PMVs@siRNA NP complexes can serve as a promising biological delivery system for treating kidney diseases.

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