Hyaluronic acid-coated zein nanoparticle-mediated resveratrol therapy for the reduction of cisplatin-associated nephrotoxicity

Abstract

Cisplatin (CDDP) is commonly used as an anticancer drug in clinical practice, but severe nephrotoxicity restricts it from exerting anticancer effects. Natural drugs, such as resveratrol, can alleviate the side effects of cisplatin, but their low solubility and gastrointestinal effects prevent them from working. Herein, we developed nanoparticles for kidney injury consisting of a biocompatible material, zein, as a carrier. HA-Zein/Res NPs were fabricated using low-molecular-weight hyaluronic acid coatings. This preparation is non-cytotoxic to renal tubular epithelial cells and can be used with confidence. Low-molecular-weight hyaluronic acid has inflammation-targeting properties and CDDP damage causes renal inflammation. Owing to this property of the low-molecular-weight hyaluronic acid coating, in vivo imaging experiments in mice demonstrated that the HA-Zein/Res NPs enabled more nanoparticles to accumulate in the renal sites affected by inflammation. Efficient resveratrol delivery alleviated kidney injury, and experiments demonstrated that HA-Zein/Res NPs could treat kidney injury while reducing the serum creatinine and urea nitrogen levels in mice. Collectively, these results indicated that this nanomaterial is a promising agent for reducing the clinical nephrotoxicity of cisplatin.