Visualized Podocyte-Targeting And Focused Ultrasound Responsive Glucocorticoid Nano-Delivery System Against Immune-Associated Nephropathy Without Glucocorticoid Side Effect

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-alpha), 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-alpha), 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-alpha 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-alpha, and no severe side effects were detected. Furthermore, Dex/PFP@LIPs-BMS-alpha, 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-alpha as effective and safe against immune-associated nephropathy.