State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau, China.
Key Laboratory of Oilseeds Processing of Ministry of Agriculture, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, Hubei, China.
J Nanobiotechnology. 2024 Sep 11;22(1):554. doi: 10.1186/s12951-024-02796-8.
Myocardial infarction (MI) is the main contributor to most cardiovascular diseases (CVDs), and the available post-treatment clinical therapeutic options are limited. The development of nanoscale drug delivery systems carrying natural small molecules provides biotherapies that could potentially offer new treatments for reactive oxygen species (ROS)-induced damage in MI. Considering the stability and reduced toxicity of gold-phenolic core-shell nanoparticles, this study aims to develop ellagic acid-functionalized gold nanoparticles (EA-AuNPs) to overcome these limitations.
We have successfully synthesized EA-AuNPs with enhanced biocompatibility and bioactivity. These core-shell gold nanoparticles exhibit excellent ROS-scavenging activity and high dispersion. The results from a label-free imaging method on optically transparent zebrafish larvae models and micro-CT imaging in mice indicated that EA-AuNPs enable a favorable excretion-based metabolism without overburdening other organs. EA-AuNPs were subsequently applied in cellular oxidative stress models and MI mouse models. We found that they effectively inhibit the expression of apoptosis-related proteins and the elevation of cardiac enzyme activities, thereby ameliorating oxidative stress injuries in MI mice. Further investigations of oxylipin profiles indicated that EA-AuNPs might alleviate myocardial injury by inhibiting ROS-induced oxylipin level alterations, restoring the perturbed anti-inflammatory oxylipins.
These findings collectively emphasized the protective role of EA-AuNPs in myocardial injury, which contributes to the development of innovative gold-phenolic nanoparticles and further advances their potential medical applications.
心肌梗死（MI）是大多数心血管疾病（CVDs）的主要诱因，而现有的治疗方法有限。携带天然小分子的纳米级药物输送系统的发展为活性氧（ROS）诱导的 MI 损伤提供了生物治疗的可能性，从而为其提供了新的治疗方法。考虑到金-酚核壳纳米粒子的稳定性和降低的毒性，本研究旨在开发鞣花酸功能化的金纳米粒子（EA-AuNPs）来克服这些限制。
我们成功地合成了具有增强的生物相容性和生物活性的 EA-AuNPs。这些核壳金纳米粒子表现出优异的 ROS 清除活性和高分散性。在光学透明斑马鱼幼虫模型上的无标记成像方法和小鼠微 CT 成像的结果表明，EA-AuNPs 能够实现基于有利排泄的代谢，而不会对其他器官造成过重负担。随后，将 EA-AuNPs 应用于细胞氧化应激模型和 MI 小鼠模型中。我们发现它们可以有效抑制凋亡相关蛋白的表达和心脏酶活性的升高，从而改善 MI 小鼠的氧化应激损伤。进一步研究脂质氧化物谱表明，EA-AuNPs 可能通过抑制 ROS 诱导的脂质氧化物水平变化来减轻心肌损伤，恢复失调的抗炎脂质氧化物。
这些发现共同强调了 EA-AuNPs 在心肌损伤中的保护作用，为创新的金-酚纳米粒子的开发做出了贡献，并进一步推进了它们在医学上的潜在应用。
