Visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system against immune-associated nephropathy without glucocorticoid side effect.
Visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system against immune-associated nephropathy without glucocorticoid side effect.
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可视化足细胞靶向和聚焦超声响应糖皮质激素纳米递送系统对抗免疫相关肾病且无糖皮质激素副作用
DOI：
10.7150/thno.53083
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发表时间：
2021
期刊：
影响因子：
12.4
通讯作者：
Zhong L
中科院分区：
文献类型：
--
作者：
Fan K;Zeng L;Guo J;Xie S;Yu Y;Chen J;Cao J;Xiang Q;Zhang S;Luo Y;Deng Q;Zhou Q;Zhao Y;Hao L;Wang Z;Zhong L
糖皮质激素广泛用于治疗肾炎，然而，其剂量依赖性副作用，如感染和代谢紊乱的风险增加，阻碍了其临床应用。本研究报道了一种可视化的足细胞靶向和聚焦超声响应的糖皮质激素纳米给药系统（Dex/PFP@LIPs-BMS-α），其特异性地将地塞米松（Dex）递送至足细胞靶点，并减少全身副作用。方法：采用声乳化法制备糖皮质激素纳米给药系统。这种糖皮质激素纳米递送系统使用合成化合物BMS-470539（BMS-α）作为"导航器"，以特异性识别和靶向足细胞上的黑皮质素-1受体（MC-1R）。负载的全氟戊烷（PFP）在低强度聚焦超声（LIFU）的配合下，通过超声靶向微泡破坏（UTMD）技术实现定向"爆炸效应"，完全释放Dex。结果如下：体外和体内实验均表明，Dex/PFP@LIPs-BMs-α准确地聚集到足细胞靶点并改善足细胞形态。此外，在体内，Dex/PFP@LIPs-BMS-α治疗组的蛋白尿和血清肌酐水平显著降低，未检测到严重的副作用。此外，Dex/PFP@LIPs-BMS-α具有超声、光声和荧光成像能力，可提供个性化的视觉指导和治疗监测。结论：本研究为Dex/PFP@LIPs-BMS-α治疗免疫相关性肾病提供了一种有效、安全的策略。
Glucocorticoids are widely used in the treatment of nephritis, however, its dose-dependent side effects, such as the increased risk of infection and metabolic disturbances, hamper its clinical use. This study reports a visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system (named as Dex/PFP@LIPs-BMS-α), which specific delivers dexamethasone (Dex) to podocyte targets and reduces systemic side effects. Methods: The glucocorticoid nano-delivery system was synthesized by a lipid thin film and a simple facile acoustic-emulsification method. This glucocorticoid nano-delivery system used BMS-470539 (BMS-α), a synthetic compound, as a “navigator” to specifically identify and target the melanocortin-1 receptor (MC-1R) on podocytes. The loaded perfluoropentane (PFP) realizes the directed "explosion effect" through ultrasound-targeted microbubble destruction (UTMD) technology under the coordination of low intensity focused ultrasound (LIFU) to completely release Dex. Results: Both in vitro and in vivo experiments have demonstrated that Dex/PFP@LIPs-BMs-α accurately gathered to podocyte targets and improved podocyte morphology. Moreover, in vivo, proteinuria and serum creatinine levels were significantly reduced in the group treated with Dex/PFP@LIPs-BMS-α, and no severe side effects were detected. Furthermore, Dex/PFP@LIPs-BMS-α, with capabilities of ultrasound, photoacoustic and fluorescence imaging, provided individualized visual guidance and the monitoring of treatment. Conclusion: This study provides a promising strategy of Dex/PFP@LIPs-BMS-α as effective and safe against immune-associated nephropathy.