Abstract

Adipokines sit at the crossroads of metabolic status and cancer biology. In obesity, elevated leptin and reduced 
adiponectin converge with chronic low-grade inflammation to remodel the tumor microenvironment toward 
angiogenesis, immune evasion, fibrosis, and metabolic plasticity. Nanoparticles can intervene directly in this 
signaling economy by concentrating modulators of adipokine pathways in adipose depots and tumors, shielding 
labile nucleic acids that edit receptor or downstream effectors, and timing release to microenvironmental 
triggers such as pH, reactive oxygen species, or matrix proteases. This review synthesizes the rationale and 
design space for nanoparticle-mediated regulation of leptin, adiponectin, and allied adipokines, from ligand or 
receptor blockade and biased agonism to gene silencing and mRNA restoration. It details lipid, polymeric, 
biomimetic, and hybrid platforms that steer payloads to adipocytes, tumor cells, endothelium, and myeloid 
populations prominent in obese hosts, and it outlines pharmacokinetic, safety, and manufacturing considerations 
that are specific to dyslipidemia and fatty liver disease. By aligning nanocarrier physicochemistry and targeting 
ligands with the signatures of the obese microenvironment, adipokine-centric nanotherapy can suppress 
tumorigenesis and resensitize cancers to standard immuno- and cytotoxic therapies.