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用于肥胖症免疫治疗的金纳米双棱锥介导的脂肪细胞凋亡伪装

Gold Nanobipyramid-Mediated Apoptotic Camouflage of Adipocytes for Obesity Immunotherapy.

作者信息

Yan Jiao, Wang Yanjing, Mu Zhengzhi, Han Xiaoqing, Bi Luopeng, Wang Xingbo, Song Panpan, Kang Yaqing, Wang Lulu, Zhang Xueyan, Wang Yanbo, Zhang Haiyuan

机构信息

Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.

Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, Changchun, 130022, China.

出版信息

Adv Mater. 2023 Feb;35(8):e2207686. doi: 10.1002/adma.202207686. Epub 2022 Dec 25.

Abstract

Obesity treatment is a global public health challenge due to inadequate weight loss and weight regain even after endeavors with multimodal treatments. Considering the abundance of resident macrophages in adipose tissues, precise regulation of the interactions between macrophages and adipocytes may provide chances for immunotherapy of obesity. Herein, inspired by the phagocytosis of macrophages to clear apoptotic cells in homeostasis, an immunotherapy strategy for obesity treatment is proposed for the first time through apoptotic camouflage of adipocytes by Au BPs to activate macrophages for clearance, where Au BPs are gold nanobipyramids engineered with adipose-targeting and apoptotic cell-mimicking functions. During clearance, the macrophage is switched from pro-inflammatory M1 to anti-inflammatory M2, remarkably modulating the immune microenvironment of adipose tissues to prevent weight regain. After inguinal injection with Au BPs, the body weights of obese mice are effectively decreased by 24.4% and can be decreased by 33.3% when combined with photothermal lipolysis, and little weight regain is associated with these treatments. This study demonstrates that the strategy of camouflaging adipocytes with apoptotic features holds great potential for obesity immunotherapy.

摘要

肥胖治疗是一项全球性的公共卫生挑战,因为即使采用多模式治疗方法,减肥效果仍不充分,且体重容易反弹。考虑到脂肪组织中存在大量驻留巨噬细胞,精确调节巨噬细胞与脂肪细胞之间的相互作用可能为肥胖的免疫治疗提供机会。在此,受巨噬细胞在体内平衡过程中吞噬清除凋亡细胞的启发,首次提出了一种肥胖治疗的免疫治疗策略,即通过金纳米双锥(Au BPs)对脂肪细胞进行凋亡伪装,以激活巨噬细胞进行清除,其中Au BPs是具有脂肪靶向和凋亡细胞模拟功能的工程化金纳米双锥。在清除过程中,巨噬细胞从促炎性M1型转变为抗炎性M2型,显著调节脂肪组织的免疫微环境,防止体重反弹。腹股沟注射Au BPs后,肥胖小鼠的体重有效降低了24.4%,与光热脂解联合使用时可降低33.3%,且这些治疗几乎不会导致体重反弹。这项研究表明,用凋亡特征伪装脂肪细胞的策略在肥胖免疫治疗中具有巨大潜力。

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