背景:阿苯达唑(ABZ)和atovaquone(ATO)通过抑制能量代谢实现对细粒棘球蚴(Egs)的杀伤功效,但是它们的利用率很低。本研讨旨在剖析ABZ-ATO负载纳米粒(ABZ-ATONPs)对Egs的杀伤功效。
方法:通过紫外光谱和纳米颗粒尺寸电位计评估了NPs的物理化学性质。体外实验展示了ATO的功效,ABZ,或ATO-ABZNPs对原头肌活动的影响,药物对肝细胞LO2,ROS产生的毒性,和能量代谢指标(乳酸脱氢酶,乳酸,丙酮酸,和ATP)。Egs感染小鼠模型的体内显示ATO的功效,ABZ,或ATO-ABZNPs对囊泡生长和器官毒性的影响。
结果:药物NP的特征是粒径均匀,稳定性,高载药量,和-21.6mV的ζ电位。ABZ或ATONP在抑制原头节活性方面比游离药物更有效。ATO-ABZNPs的原头肌杀伤作用强于游离药物。体内Egs感染小鼠实验表明,ATO-ABZNPs可以减少囊泡的大小,并可以保护各种器官。能量代谢结果显示ATO-ABZNPs显著提高了ROS水平和丙酮酸含量,乳酸脱氢酶减少,乳酸含量,和幼虫的ATP生产。此外,ATO-ABZNPs促进了DHODH蛋白表达的降低。
结论:ATO-ABZNP在体外和体内表现出抗CE,可能通过抑制能量产生和促进丙酮酸聚集。
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.
CONCLUSIONS: ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.