Innovative Drug Delivery System Holds Promise for Treating Obesity and Its Complications
A research team from the Li Ka Shing Faculty of Medicine at the Chinese University of Hong Kong has developed a new delivery system for thyroid hormone (TH) using nanoparticles modified with an adipose-homing peptide.
This system selectively transports TH to adipose tissues, which could advance the treatment of obesity-related medical complications and reduce the adverse effects caused by systemic administration of TH. The study results have been published in Nature Communications.
While TH has therapeutic potential for treating obesity by targeting thermogenesis to promote energy expenditure, clinical trials have failed to demonstrate obvious clinical benefits from the chronic systemic administration of TH on weight loss in obese individuals. Additionally, widespread expression of TH receptors often leads to serious deleterious effects on multiple organs, such as tachycardia, heart attack, muscle wasting, and osteoporosis.
TH-encapsulated nanoparticles were modified with an adipose-homing peptide to selectively deliver TH to adipose tissues. Adipose-targeted delivery of TH was found to be substantially more potent than systemic TH therapy in reducing obesity and related metabolic complications, without causing adverse effects on non-adipose tissues.
The study also revealed that adipose-targeted TH therapy could convert “bad” white fat to “good” brown fat, which burns calories by creating heat. In contrast, systemic TH therapy cannot induce the “browning” of white fat due to its suppression of sympathetic nerves.
The research team also discovered that adipose-targeted delivery of TH effectively alleviates hypercholesterolemia and atherosclerosis, major causes of coronary heart disease and ischemic stroke.
“This is the first proof-of-concept study showing that nanoparticle-based targeted delivery of TH to adipose tissue is an effective and safe pharmacotherapy for obesity and its related cardiometabolic complications. The findings have also resolved a long-standing mystery of why systemic TH therapy failed to reduce body weight,” said Professor Xu Aimin, research director.
