Biomaterial-enables targeted drug delivery for obesity: Adipose-targeted nanocarriers and tissue-specific therapies

Biomaterial-enabled targeted drug delivery represents a transformative approach for treating obesity by exploiting the unique structural and metabolic characteristics of adipose tissue in vascular density, immunological composition, and thermogenic function, offering depot-specific opportunities for therapeutic intervention. Advances in nanocarrier engineering including lipid nanoparticles, polymeric nanoparticles, and liposomes now enable precise delivery of thermogenic agents, anti-inflammatory compounds, and gene modulators to adipose depots. Surface functionalization with peptides, antibodies, or glycans enhances targeting specificity toward markers such as prohibitin, VEGFR2, β3-adrenergic receptors, and macrophage-associated receptors. These engineered systems support mechanisms such as WAT browning, immunomodulation, and controlled drug release, collectively improving metabolic homeostasis. Preclinical studies using diet-induced obese mice and larger animal models have demonstrated favorable biodistribution, safety, and metabolic outcomes, supported by biomarkers including UCP1 expression, macrophage polarization, and systemic metabolic indices. Despite significant progress, challenges remain in manufacturing scalability, immunogenicity reduction, and navigating evolving regulatory requirements. Overall, adipose-targeted biomaterial platforms represent a rapidly advancing field, and this review provides a mechanistic, depot-specific, and translational framework to enhance therapeutic outcomes for obesity with strong potential to enhance therapeutic outcomes for obesity and related metabolic disorders.