Qiaqia Xiao, Lu Tang, Siying Chen, Yijun Mei, Chuying Wang, Jing Yang, Jing Shang, Shengliang Li, Wei Wang
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引用次数: 0
摘要
脂肪过度堆积和慢性炎症是肥胖症的两个典型特征。AMP 激活蛋白激酶(AMPK)是能量代谢的主要调节因子,参与脂肪组织(AT)的脂肪生成、脂肪生成和炎症调节。因此,通过 AMPK 调节有效降脂和抗炎在治疗肥胖症中发挥着至关重要的作用。本文通过在光热剂黑磷纳米片(BP)上附着聚二甲双胍(PolyMet),制备了一种抗肥胖纳米夹层。PolyMet 可激活 AMPK,从而抑制脂肪生成,促进褐变,并通过减少巨噬细胞浸润、使巨噬细胞表型恢复极性和下调促炎细胞因子来缓解 AT 炎症。此外,BP 还能通过光热效应诱导脂肪细胞和巨噬细胞的脂肪分解和凋亡。通过使用透明质酸(HA)和 MMP2 底物连接的 P3 肽修饰 HA(P3-HA)进行进一步功能化,P3 和 HA 的双重靶向作用以及 MMP2 切割后 HA 介导的 CD44 聚簇作用增强了抗肥胖效果。在激光照射下,所设计的纳米三明治(P3-HA/PM@BP)能有效抑制肥胖小鼠的肥胖发展,提高AT中的M2/M1比率,降低血清中胆固醇/甘油三酯的水平,并改善胰岛素敏感性,为促进现代抗肥胖疗法的临床开发展现了良好的研究潜力。
Two-Pronged Attack: Dual Activation of Fat Reduction Using Near-Infrared-Responsive Nanosandwich for Targeted Anti-Obesity Treatment.
Excessive fat accumulation and chronic inflammation are two typical characteristics of obesity. AMP-activated protein kinase (AMPK), a master regulator of energy metabolism, is involved in adipogenesis, lipogenesis, and inflammation modulation in adipose tissue (AT). Thus, effective lipid reduction and anti-inflammation through AMPK regulation play vital roles in treating obesity. Herein, an anti-obesity nanosandwich is fabricated through attaching polymetformin (PolyMet) onto photothermal agent black phosphorus nanosheets (BP). PolyMet activates AMPK to inhibit adipogenesis, promote browning, and mitigate AT inflammation by decreasing macrophage infiltration, repolarizing macrophage phenotype, and downregulating pro-inflammatory cytokines. Additionally, BP induces lipolysis and apoptosis of adipocytes and macrophages through a photothermal effect. By further functionalization using hyaluronic acid (HA) and MMP2 substrate-linking P3 peptide-modified HA (P3-HA), an enhanced anti-obesity effect is obtained by dual-targeting of P3 and HA, and HA-mediated CD44 poly-clustering after MMP2 cleavage. Upon laser irradiation, the designed nanosandwich (P3-HA/PM@BP) effectively inhibits obesity development in obese mice, increases M2/M1 ratio in AT, reduces the serum levels of cholesterol/triglyceride and improves insulin sensitivity, exhibiting promising research potential to facilitate the clinical development of modern anti-obesity therapies.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.