Abstract

Obesity is accompanied by a state of chronic low-grade inflammation that is primarily driven by immune cell 
dysfunction within adipose tissue. Among these immune cells, macrophages play a central role by undergoing 
phenotypic polarization that dictates inflammatory outcomes. In lean adipose tissue, macrophages 
predominantly exhibit an anti-inflammatory M2 phenotype, whereas obesity promotes a shift toward the pro
inflammatory M1 phenotype, sustaining tissue inflammation and metabolic dysfunction. Conventional anti
inflammatory therapies lack the specificity required to selectively reprogram macrophage phenotypes within 
adipose tissue, limiting their clinical efficacy. Nanocarrier-based drug delivery systems have emerged as 
powerful tools to overcome these limitations by enabling targeted modulation of macrophage polarization. This 
review critically examines the mechanisms underlying macrophage polarization in obesity-driven inflammation 
and highlights recent advances in nanocarrier-mediated strategies to reprogram macrophage phenotypes. We 
discuss the design principles of nanocarriers, therapeutic payloads, targeting strategies, and biological 
challenges associated with this approach. Finally, we explore emerging opportunities and translational prospects 
for nanotechnology-enabled immunometabolic therapies aimed at resolving chronic inflammation in obesity.