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.
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。