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.