肝癌与发病率和死亡率显着相关。低强度超声与纳米药物输送系统的结合有望成为肝癌治疗的替代方案。本研究重点关注叶酸（FA）修饰纳米颗粒的利用，该纳米颗粒负载有荧光染料 DiR 和液体碳氟化合物（PFP）。这些纳米颗粒具有增强超声刺激下肝癌靶向性和未来体内应用的潜力。研究了叶酸修饰的Crebanine聚乙二醇-聚乳酸共聚物纳米颗粒（FA-Cre@PEG-PLGA NPs）的药代动力学和组织分布。评估了药代动力学参数、肝脏靶向和体内分布。此外，体外研究了FA-Cre@PEG-PLGA NPs联合超声波照射对小鼠肝癌H22细胞增殖和急性毒性的抑制作用。分别利用小动物体内成像系统和原位肝细胞癌移植模型评估了 FA-Cre@PEG-PLGA NPs 的肿瘤靶向和抗肿瘤功效。药代动力学研究和组织分布测试表明 FA-Cre @PEG-PLGA NPs显着延长了药物在大鼠体内的半衰期和保留时间，肝脏靶向作用明显。此外，体内急性毒性试验表明FA-Cre@PEG-PLGA NPs不良反应极小，能够达到减毒目的。动物实验结果进一步证实FA-Cre@PEG-PLGA NPs在肿瘤部位的保留时间更长、抗肿瘤效果更佳、对肝肾组织损伤更小。超声照射下的 PEG-PLGA NP 在体内表现出卓越的安全性和强大的抗肿瘤功效，为通过超声技术与纳米药物输送系统相结合来治疗肝癌提供了一种有前景的治疗策略。© 2024 Cheng 等人。

Liver cancer is associated significantly with morbidity and mortality. The combination of low-intensity ultrasound with nanomedicine delivery systems holds promise as an alternative for the treatment for liver cancer. This study focuses on the utilization of folic acid (FA) modified nanoparticles, which are loaded with fluorescent dye DiR and liquid fluorocarbon (PFP). These nanoparticles have the potential to enhance liver cancer targeting under ultrasound stimulation and future applications in vivo.The pharmacokinetics and tissue distribution of folic acid-modified Crebanine polyethylene glycol-polylactic acid copolymer nanoparticles (FA-Cre@PEG-PLGA NPs) were investigated. The pharmacokinetic parameters, liver targeting, and in vivo distribution were assessed. Additionally, the inhibitory impacts of FA-Cre@PEG-PLGA NPs in combination with ultrasonic irradiation on the proliferation and acute toxicity of H22 cells of mouse hepatoma were investigated in vitro. The tumor targeting and anti-tumor efficacy of FA-Cre@PEG-PLGA NPs were assessed utilizing a small animal in vivo imaging system and an in situ hepatocellular carcinoma transplantation model, respectively.The pharmacokinetic studies and tissue distribution tests demonstrated that FA-Cre@PEG-PLGA NPs conspicuously prolonged the half-life and retention time of the drug in rats, and the liver targeting effect was pronounced. Additionally, the in vivo acute toxicity test indicated that FA-Cre@PEG-PLGA NPs had minimal adverse reactions and could fulfill the aim of attenuating the drug. The outcomes of the animal experiments further substantiated that FA-Cre@PEG-PLGA NPs had a longer retention time at the tumor site, a superior anti-tumor effect, and less damage to liver and kidney tissue.The integration of FA-Cre@PEG-PLGA NPs with ultrasound irradiation demonstrated exceptional safety and potent anti-tumor efficacy in vivo, presenting a promising therapeutic strategy for the treatment of liver cancer through the combination of ultrasound technology with a nanomedicine delivery system.© 2024 Cheng et al.