Adipocyte-Targeted Nanocomplex with Synergistic Photothermal and Pharmacological Effects for Combating Obesity and Related Metabolic Syndromes
Yuanyuan Zhang,
Xiaojiao Zeng,
Fan Wu,
Xiaopeng Yang,
Tingting Che,
Yin Zheng,
Jie Li,
Yufei Zhang,
Xinge Zhang,
Zhongming Wu
Affiliations
Yuanyuan Zhang
NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China
Xiaojiao Zeng
NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China
Fan Wu
Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin 300131, China
Xiaopeng Yang
NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China
Tingting Che
NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China
Yin Zheng
Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
Jie Li
Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Yufei Zhang
Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Xinge Zhang
Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Zhongming Wu
NHC Key Laboratory of Hormones and Development, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China
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 PPARγ/PGC1α and HSF1/PGC1α, 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.
