Mohaghegh Neda, Iyer Anjali, Wang Ethan, Balajam Narges Zargar, Kang Heemin, Akbari Mohsen, Barnhill Michele S, Khademhosseini Ali, Pearson Ryan M, Hassani Najafabadi Alireza
Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA.
Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA.
J Control Release. 2025 Jun 10;382:113670. doi: 10.1016/j.jconrel.2025.113670. Epub 2025 Apr 3.
Obesity is characterized by a significant imbalance in adipose tissue macrophages (ATMs), shifting from anti-inflammatory M2 to pro-inflammatory M1 phenotypes, contributing to chronic low-grade inflammation and metabolic dysfunction. This study explores the potential of nanoparticle (NP)-mediated immunomodulation to address obesity-related inflammation, adipocyte browning, and metabolic dysfunction. Apigenin (Api), a natural compound with notable anti-inflammatory properties, was encapsulated within poly(lactic-co-glycolic acid) (PLGA) NPs (Api-NPs) for localized delivery to adipose tissues (ATs). Api-NPs demonstrated favorable physicochemical properties and sustained release profiles. In vitro, Api-NPs, increased M2 macrophage (MΦ) polarization, reduced inflammatory markers, and promoted adipocyte browning. In a high-fat diet (HFD)-induced obesity mouse model, Api-NP administration effectively modulated MΦ polarization and enhanced AT browning, leading to marked reductions in body weight and AT mass. Our findings indicate that Api-NP treatment mitigates obesity-related inflammation and promotes beneficial changes in AT composition and function. Importantly, histological evaluations confirmed the absence of toxicity in major organs, reinforcing the safety profile of this approach. These results position Api-NPs as a promising novel therapeutic strategy for obesity management, integrating immune modulation and localized drug delivery to address the complexities of obesity and its associated inflammatory processes.
肥胖的特征是脂肪组织巨噬细胞（ATM）严重失衡，从抗炎的M2表型转变为促炎的M1表型，导致慢性低度炎症和代谢功能障碍。本研究探讨了纳米颗粒（NP）介导的免疫调节在解决肥胖相关炎症、脂肪细胞褐变和代谢功能障碍方面的潜力。芹菜素（Api）是一种具有显著抗炎特性的天然化合物，被包裹在聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒（Api-NPs）中，用于局部递送至脂肪组织（AT）。Api-NPs表现出良好的物理化学性质和缓释特性。在体外，Api-NPs增加了M2巨噬细胞（MΦ）极化，降低了炎症标志物，并促进了脂肪细胞褐变。在高脂饮食（HFD）诱导的肥胖小鼠模型中，给予Api-NPs可有效调节MΦ极化并增强AT褐变，导致体重和AT质量显著降低。我们的研究结果表明，Api-NP治疗可减轻肥胖相关炎症，并促进AT组成和功能的有益变化。重要的是，组织学评估证实主要器官无毒性，加强了该方法的安全性。这些结果使Api-NPs成为一种有前途的肥胖管理新治疗策略，整合免疫调节和局部药物递送以解决肥胖及其相关炎症过程的复杂性。
