Adipose tissue-targeted drug delivery for treating obesity: current opportunities and challenges.

Obesity has emerged as a global public health crisis in the 21st century, with its prevalence continuing to rise worldwide. Beyond its well-established links to metabolic diseases (diabetes, hypertension, dyslipidemia, and cardiovascular disease), obesity correlates significantly with oncological and musculoskeletal morbidity. Researchers have discovered that converting energy-storing white adipose tissue (WAT) into energy-expending thermogenic fat through external stimuli or browning agents-a process termed 'white fat browning'-has become a novel therapeutic strategy for obesity and its complications. This transformation is mediated by the activation of key factors such as uncoupling protein 1 (UCP1), which promotes thermogenesis and energy expenditure in adipocytes, thereby reducing fat accumulation. Studies have shown that certain pharmacological agents (e.g. β3-adrenergic receptor agonists) or natural compounds (e.g. resveratrol, capsaicin) can effectively induce white fat browning. However, systemic administration of these agents may cause off-target effects, such as cardiovascular overstimulation or metabolic disturbances, significantly limiting their clinical application. To address this challenge, adipose tissue-targeted drug delivery systems have been developed. These systems utilize either the unique microenvironment of adipose tissue (e.g. specific receptor expression) or nanocarrier technologies (e.g. polymeric nanoparticles) to precisely deliver browning agents to target fat depots. This review summarizes recent advances in targeted delivery vectors for obesity treatment via white fat browning, while also discussing challenges in nanomaterial design, targeting strategy optimization, and clinical translation.