Photosensitive Biomimetic Nanomedicine-Mediated Recombination of Adipose Microenvironments for Antiobesity Therapy

Abstract

Obesity-induced insulin resistance is a hallmark of metabolic syndrome, and chronic low-grade inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells. Current treatments are lacking in efficacy and immunosuppression. Therefore, novel therapies are needed to prevent chronic inflammation and alleviate obesity-related insulin resistance. In this work, novel red light-responsive biomimetic nanoparticles (RSCP NPs) are reported to perform targeted delivery of multiple drugs and effectively reduce nonspecific enrichment. These results showed that the dual-targeting and multiple-signaling response (red light signaling and different pH microenvironments) of the RSCP NPs enabled the precise delivery of astaxanthin (Asta) and rosiglitazone (Rosi) to M1-like macrophages and white adipocytes, respectively, to alleviate the low-grade inflammation of white adipose tissue (WAT) and promote white adipocyte browning. Moreover, RSCP NPs-mediated Asta and Rosi treatment robustly alleviated insulin resistance and other metabolic disorders in the obese animal models (high-fat diet (HFD)-induced or genetically obese mice). Overall, this study provides a theoretical and practical basis for the development and application of novel drug delivery systems for metabolic diseases by elucidating the synergistic long-term targeting mechanism and target molecule stability of red light-sensitive bionic nanodrug delivery systems.