Abstract

Obesity-induced type 2 diabetes mellitus (T2DM) is a growing global health concern driven by chronic low
grade inflammation, insulin resistance, and impaired metabolic homeostasis. Conventional therapies such as 
lifestyle interventions, antidiabetic drugs, and bariatric surgery offer only partial benefits and are limited by 
poor long-term compliance, side effects, and relapse of metabolic dysfunction. In recent years, nanotechnology
based immunotherapeutics particularly nanovaccines and immunomodulatory nanoparticles have emerged as 
promising strategies for tackling the underlying immunometabolic derangements that link obesity to T2DM. 
Nanovaccines are designed to induce protective immune responses against obesity-associated inflammatory 
mediators or to enhance tolerance to metabolic antigens, thereby restoring immune balance. 
Immunomodulatory nanoparticles, on the other hand, can reprogram immune cells such as macrophages, 
dendritic cells, and T lymphocytes to reduce systemic inflammation and improve insulin sensitivity. These 
nanoplatforms can be engineered for targeted delivery, controlled release, and co-delivery of antigens with 
adjuvants, enabling precise modulation of the immune system. Preclinical studies have demonstrated that such 
nanomedicines attenuate adipose tissue inflammation, preserve pancreatic β-cell function, and improve glucose 
homeostasis. However, challenges such as biosafety, large-scale production, regulatory approval, and long-term 
immunological consequences remain to be addressed before clinical translation. This review provides a 
comprehensive overview of the mechanisms, design principles, recent advances, and future directions of 
nanovaccines and immunomodulatory nanoparticles in preventing obesity-induced diabetes. 
Keywords: nanovaccines, immunomodulatory nanoparticles, obesity-induced diabetes, metabolic inflammation, 
immunotherapy