NIR-activated adipose-targeted nanocarrier drives local browning and metabolic restoration

Abstract The escalating global prevalence of obesity and its associated metabolic disorders now represents one of the most urgent public health crises. Despite the pressing need for safe and effective anti-obesity interventions, current therapeutic options are often limited by suboptimal efficacy and various side effects. Herein, we present a microneedle (MN)-based drug delivery platform, termed RES@hmPDA-Dpep/MN, for photothermal browning therapy (PBT) to combat obesity. This system integrates hemispherical mesoporous polydopamine (hmPDA) nanoparticles with resveratrol (RES) and an adipose-homing peptide (Dpep) for localized PBT. Under identical conditions, hmPDA maintains photothermal performance comparable to spherical mPDA, while exhibiting advantageous drug-loading behavior, particularly under higher drug-feeding conditions. In addition, the platform supports localized delivery with near-infrared-triggered, on-demand RES release and thermogenic activation. In vivo studies demonstrate that the RES@hmPDA-Dpep/MN system effectively suppresses white adipose tissue expansion, reduces body weight by 16.1 ± 2.5%, and significantly improves obesity-associated metabolic dysfunctions, including hyperlipidemia and hepatic steatosis. Mechanistic analyses reveal marked upregulation of uncoupling protein 1 (UCP1) and other key browning genes. Furthermore, the nanoplatform shows favorable in vitro biocompatibility and hemocompatibility, supporting its potential for further translational evaluation. Collectively, this PBT strategy may serve as a potential localized intervention for fat reduction and systemic metabolic improvement in the management of obesity and related metabolic disorders.