Peptide-functionalized gold nanoparticles lowered diet-induced obesity in rats by reducing white adipose tissue mass

Abstract

Anti-obesity drugs are limited in their application due to poor drug specificity, efficacy, and bystander side effects. The study reports on the use of bi-functionalized gold nanoparticles (AuNPs) to improve the selectivity and efficacy of therapeutic agents in obese male Wistar rats. Citrate-capped AuNPs (cAuNPs) were functionalized with Adipose Homing Peptide (AHP) and with or without a D(KLAKLAK)2 peptide (KLA); i.e., AuNP-AHP-KLA and AuNP-AHP, respectively. The rats were grouped into lean (low fat, LF), obesity-resistant (high fat, HF1), and three groups (HF2, HF3 and HF4) from obesity-prone rats. Rats were intravenously injected every third day for four weeks with their respective treatments; phosphate buffered saline (LF and HF2), AuNP-AHP-KLA (HF1 and HF4), and AuNP-AHP (HF3). Urinalysis was performed during the first and the fourth week of treatments. Oral Glucose Tolerance Test (OGTT) was performed after the third week of treatment. AuNPs distribution in white adipose tissues (WATs) and the liver of rats on HF1, HF3 and HF4 groups was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Treatment with AuNP-AHP-KLA (HF4) reduced the body weight and adipose tissue mass of the obese rats in HF4, and improved their glucose tolerance. Urinalysis showed that the AuNPs conjugates did not cause any toxicity to the rats after four weeks of treatment. High content of gold (Au) was detected in the WATs of HF3 group treated with AuNP-AHP, and negligible amount of Au was found in the HF1 and HF4 groups treated with AuNP-AHP-KLA. The preliminary data confirmed that bifunctionalized-AuNPs can potentially be effective theranostic tools for obesity treatment. Further studies are underway to determine the histological and molecular effects of this targeted nanotherapy.