Department of Ultrasound, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People's Republic of China.
Department of Ultrasound, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People's Republic of China.
Int J Nanomedicine. 2020 Oct 2;15:7315-7327. doi: 10.2147/IJN.S262052. eCollection 2020.
To investigate the antifibrotic effect of the combination of a PPARγ agonist-loaded nanoparticle-microbubble complex with ultrasound (US) exposure on renal interstitial fibrosis (RIF).
Polylactide-co-glycolide (PLGA) nanoparticles were used to load PPARγ agonist (rosiglitazone, RSG) and prepare PLGA-RSG nanoparticles (PLNPs-RSG); then, a novel complex between PLNPs-RSG and SonoVue microbubbles (MBs) (PLNPs-RSG-MBs) was prepared. The size distribution, zeta potentials, RSG-loading capacity and entrapment efficiency were measured, and the release of RSG was assessed using a UV-vis spectrophotometer. The in vitro cytotoxicity and in vivo systemic toxicity assays were performed. The cellular uptake assessment was performed using a confocal laser scanning microscope (CLSM). The in vivo biodistribution assessment was performed using fluorescence imaging with a near-infrared (NIR) imaging system. Furthermore, this complex was administered to a unilateral ureteral obstruction (UUO) rat model with the assistance of US exposure to investigate the antifibrotic effect.
This PLNPs-RSG-MBs complex had a size of 2199.5± 988.1 nm and a drug-loading efficiency of 28.5%. In vitro cytotoxicity and in vivo systemic toxicity assays indicated that the PLNPs-RSG-MBs complex displayed excellent biocompatibility. In addition, the complex showed high cellular uptake efficiency in vitro and kidney-targeting ability in vivo. In a UUO rat model, the combination of the PLNPs-RSG-MBs complex with US exposure significantly reduced collagen deposition and successfully attenuated renal fibrosis.
The combination of the PLNPs-RSG-MBs complex with US exposure may be a promising approach for the treatment of RIF.
研究载过氧化物酶体增殖物激活受体γ（PPARγ）激动剂的纳米颗粒-微泡复合物与超声（US）联合应用对肾间质纤维化（RIF）的抗纤维化作用。
聚乳酸-羟基乙酸共聚物（PLGA）纳米粒用于负载 PPARγ 激动剂（罗格列酮，RSG），制备 PLGA-RSG 纳米粒（PLNPs-RSG）；然后，制备 PLNPs-RSG 与 SonoVue 微泡（MBs）的新型复合物（PLNPs-RSG-MBs）。测量其粒径分布、Zeta 电位、RSG 载药量和包封率，并采用紫外分光光度计评估 RSG 的释放情况。进行体外细胞毒性和体内全身毒性试验。采用共聚焦激光扫描显微镜（CLSM）评估细胞摄取情况。采用近红外（NIR）成像系统进行体内生物分布评估。此外，该复合物在超声辅助下用于单侧输尿管梗阻（UUO）大鼠模型，以研究其抗纤维化作用。
该 PLNPs-RSG-MBs 复合物的粒径为 2199.5±988.1nm，载药效率为 28.5%。体外细胞毒性和体内全身毒性试验表明，PLNPs-RSG-MBs 复合物具有良好的生物相容性。此外，该复合物在体外显示出较高的细胞摄取效率，在体内具有肾脏靶向能力。在 UUO 大鼠模型中，PLNPs-RSG-MBs 复合物联合 US 照射显著减少胶原沉积，成功减轻肾纤维化。
PLNPs-RSG-MBs 复合物联合 US 照射可能是治疗 RIF 的一种有前途的方法。
