Adipocyte-Targeted Nanocomplex with Synergistic Photothermal and Pharmacological Effects for Combating Obesity and Related Metabolic Syndromes
By
Zhang, YY (Zhang, Yuanyuan) [1] , [2] , [3] ; Zeng, XJ (Zeng, Xiaojiao) [1] , [2] , [3] ; Wu, F (Wu, Fan) [4] ; Yang, XP (Yang, Xiaopeng) [1] , [2] , [3] ; Che, TT (Che, Tingting) [1] , [2] , [3] ; Zheng, Y (Zheng, Yin) [5] , [6] ; Li, J (Li, Jie) [7] ; Zhang, YF (Zhang, Yufei) [7] ; Zhang, XG (Zhang, Xinge) [7] ; Wu, ZM (Wu, Zhongming) [1] , [2] , [3] , [5] , [6]
Volume
14Issue
16
DOI
10.3390/nano14161363
Article Number
1363
Published
AUG 2024
Indexed
2024-09-13
Document Type
Article
Jump to
Abstract
Obesity is a global epidemic which induces a multitude of metabolic disorders. Browning of white adipose tissue (WAT) has emerged as a promising therapeutic strategy for promoting weight loss and improving associated metabolic syndromes in people with obesity. However, current methods of inducing white adipose tissue browning have limited applicability. We developed a nanocomplex pTSL@(P+I), which is a temperature-sensitive liposome (TSL) surface-conjugated with an adipocyte-targeting peptide (p) and loaded with both browning-promoting agents (P) and photosensitizing agents (I). This nanocomplex exhibits adipocyte targeting, as well as synergistic pharmacological and photothermal properties to promote browning. pTSL@(P+I) effectively upregulates UCP1 and COX5B expression by activating the transcription axis of PPAR gamma/PGC1 alpha and HSF1/PGC1 alpha, thereby promoting white adipose tissue browning and reducing obesity. This novel nanocomplex exhibited a uniform spherical shape, with an average diameter of approximately 200 nm. Additionally, the nanocomplexes exhibited remarkable photothermal properties and biocompatibility. Further, when adipocytes were treated with pTSL@(P+I), their triglyceride content decreased remarkably and intracellular mitochondrial activity increased significantly. When applied to diet-induced obesity (DIO) mice, the nanocomplex exhibited significant efficacy, demonstrating a notable 14.4% reduction in body weight from the initial measurement, a decreased fat/lean mass ratio of 20.8%, and no statistically significant disparities (p > 0.05) in associated side effects when compared to the control group. In summary, implementation of the targeted nanocomplex pTSL@(P+I) to enhance energy expenditure by stimulating white adipose tissue browning offers a promising therapeutic approach for the treatment of obesity and related metabolic syndromes.