能量代谢双重调控纳米粒（阿托伐醌-阿苯达唑纳米粒）抗包虫病的疗效及机制。
Efficacy and mechanism of energy metabolism dual-regulated nanoparticles (atovaquone-albendazole nanoparticles) against cystic echinococcosis.
机构信息
First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Clinical Drug Research, Urumqi, Xinjiang, 830011, China.
出版信息
BMC Infect Dis. 2024 Aug 3;24(1):778. doi: 10.1186/s12879-024-09662-w.
BACKGROUND
Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs.
METHODS
Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity.
RESULTS
Drug NPs are characterized by uniform particle size, stability, high drug loading, and - 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes.
CONCLUSION
ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.
背景
阿苯达唑（ABZ）和阿托伐醌（ATO）通过抑制能量代谢对细粒棘球蚴（Egs）发挥杀伤作用，但利用率较低。本研究旨在分析 ABZ-ATO 载药纳米粒（ABZ-ATO NPs）对 Egs 的杀伤效果。
方法
通过紫外分光光度法和纳米粒度电位仪对 NPs 的理化性质进行评价。体外实验研究了 ATO、ABZ 或 ATO-ABZ NPs 对原头蚴活力、药物对 LO2 肝细胞毒性、ROS 生成及能量代谢指标（乳酸脱氢酶、乳酸、丙酮酸、ATP）的影响。体内 Egs 感染小鼠模型研究了 ATO、ABZ 或 ATO-ABZ NPs 对囊泡生长和器官毒性的影响。
结果
药物 NPs 具有粒径均一、稳定性好、载药量高、zeta 电位为-21.6mV 的特点。ABZ 或 ATO NPs 比游离药物更能抑制原头蚴活力。ATO-ABZ NPs 的原头蚴杀伤效果强于游离药物。体内 Egs 感染小鼠实验表明，ATO-ABZ NPs 可减小囊泡大小，并能保护各器官。能量代谢结果表明，ATO-ABZ NPs 显著提高 ROS 水平和丙酮酸含量，降低幼虫中乳酸脱氢酶、乳酸含量和 ATP 生成。此外，ATO-ABZ NPs 促进了原头蚴中二氢乳清酸脱氢酶蛋白表达的下降。
结论
ATO-ABZ NPs 具有体内外抗 CE 作用，可能通过抑制能量产生和促进丙酮酸聚集来实现。
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