Understanding obesity-cancer crosstalk to inform the immunomodulatory roles of anti-obesity nanotherapeutics.

Obesity represents a chronic inflammatory condition characterized by adipose tissue dysfunction that drives systemic metabolic derangements and promotes tumor progression. Adipose inflammation, dominated by pro-inflammatory macrophages and dysregulated adipokine secretion, not only impairs lipid metabolism but also suppresses anti-tumor immunity. Although anti-obesity medications (AOMs) can induce weight loss, their limited ability to resolve inflammation constrains long-term metabolic and oncologic benefits. Recent advances in nanomedicine have enabled targeted modulation of adipose tissue through enhanced drug bioavailability, controlled release, and remodeling of the immune microenvironment. This review summarizes recent progress in anti-inflammatory nanomedicines for obesity and their potential to synergize with cancer therapy. Specifically, we discuss nanomedicines that alleviate adipose inflammation via macrophage reprogramming, cytokine silencing, or reactive oxygen species scavenging, as well as those that promote white adipose tissue browning and brown adipose tissue activation and thermogenesis. By elucidating the interplay between adipose inflammation, metabolic regulation, and cancer immunotherapy, we propose that natural compounds and drug-free nanomaterials targeting adipose inflammation may serve as a critical foundation for next-generation nanotherapeutics, offering a dual-benefit strategy to combat obesity and enhance cancer immunotherapy efficacy.