Nanomaterials for the treatment and monitoring of obesity: Targeting adipose tissue macrophages.

Abstract

Obesity represents a growing global health crisis, closely associated with chronic low-grade inflammation driven by the recruitment and polarization of adipose tissue macrophages (ATMs). Targeting ATMs to suppress adipose inflammation has emerged as a promising strategy for obesity treatment. However, conventional anti-inflammatory therapies are hindered by poor tissue specificity and systemic side effects. In recent years, advances in nanotechnology have enabled the development of multifunctional nanomaterials capable of modulating ATM behavior with improved precision and efficacy. This review presents the first comprehensive synthesis of multimodal nano-based strategies for targeting ATMs in obesity, integrating both therapeutic and monitoring applications. We begin by elucidating the immunological roles of ATMs in the pathogenesis of obesity and associated metabolic disorders. We then outline rational design principles for ATM-targeted nanomaterials, followed by an in-depth analysis of representative organic and inorganic nanomedicines, including emerging platforms such as gene-editing systems and combination nanotherapies. Furthermore, we summarize recent developments in nano-enabled imaging strategies for non-invasive monitoring of adipose tissue inflammation. Finally, we critically discuss the key challenges-such as off-target effects and translational barriers-and propose future research directions. By bridging advances in nanomedicine and immunometabolism, this review fills a significant gap in the literature and provides a forward-looking perspective for the clinical translation of ATM-targeted nanotherapies in obesity management. STATEMENT OF SIGNIFICANCE: Obesity is a major global health burden, strongly linked to chronic low-grade inflammation mediated by adipose tissue macrophages (ATMs). While ATMs represent a promising immunotherapeutic target, effective strategies for their precise modulation remain limited. Recent advances in nanotechnology have opened new avenues for selectively targeting ATMs. However, there is a lack of comprehensive reviews integrating nanomedicine with ATM biology in the context of obesity. This review fills that critical gap by systematically summarizing design strategies for ATM-targeted nanomaterials, evaluating their therapeutic and monitoring applications, and outlining current challenges and future directions. By bridging nano-immunotherapy and metabolic disease, this work provides timely insights to guide innovation in obesity treatment and monitoring.