Self-Assembled Pt/Honokiol Nanomicelles for the Treatment of Sepsis-Associated Acute Kidney Injury.

Abstract

Sepsis is a severe and complex systemic infection that can result in multiple organ dysfunction. Sepsis-associated acute kidney injury (SAKI), caused by inflammatory response, oxidative stress, and cellular apoptosis, is a common complication that seriously impacts patient survival rates. Herein, a potent and novel metal-polyphenol nanomicelle can be efficiently self-assembled with Pt4+ and honokiol (HK) by the chelation, π-π conjugation, hydrophobic action, and the surfactant properties of Tween-80. These nanomicelles not only enhance drug bioavailability (encapsulation rates: Pt─49%, HK─70%) and reduce drug toxicity (safety dose: <20 μg/g) but also improve targeting toward damaged renal tissues. Furthermore, Pt4+ and HK in the nanomicelles exert a synergistic physiological effect by scavenging free radicals to alleviate oxidative damage, inhibiting macrophage activation and the release of inflammatory factors to regulate inflammation, and displaying broad-spectrum antimicrobial activity to control infection. These actions collectively protect renal tissue and restore its functionality. Here, we constructed metal-polyphenol nanomicelles (Pt/HK-NMs) via ingenious and efficient self-assembly, providing a new strategy to compensate for deficiencies in the hemodialysis and antibiotic treatment of SAKI.