Abstract

Obesity is a multifactorial, relapsing disease driven by complex interactions between genetics, environment, and 
behavior. Conventional systemic pharmacotherapy often fails to provide durable weight loss and is limited by 
off-target toxicity in the cardiovascular, hepatic, and central nervous systems. Precision delivery of anti-obesity 
agents to specific tissues and cell populations offers a rational strategy to increase efficacy while reducing 
adverse effects. Smart nanocarriers engineered to sense local microenvironmental cues, respond to external 
stimuli, and recognize molecular markers—are emerging as powerful tools to achieve this goal. This review 
outlines the pathophysiological rationale for targeted delivery in obesity, design principles of smart 
nanocarriers, and organ-specific targeting strategies for adipose tissue, liver, gut, and CNS. We discuss stimuli
responsive and logic-gated systems, nano-enabled delivery of small molecules, peptides, biologics, and nucleic 
acids, as well as integration with diagnostics for precision medicine. Finally, we address safety, regulatory, and 
implementation challenges that must be overcome before these technologies can be deployed in routine 
metabolic care.