叶酸修饰的克里班氨酸聚乙烯乙二醇 - 二甲基乳酸羟基乙酸共聚物共聚物纳米颗粒的药代动力学和抗肿瘤药效学的初步研究
Preliminary Study on Pharmacokinetics and Antitumor Pharmacodynamics of Folic Acid Modified Crebanine Polyethyleneglycol-Polylactic Acid Hydroxyacetic Acid Copolymer Nanoparticles
影响因子:6.50000
分区:医学2区 / 药学2区 纳米科技3区
发表日期:2024
作者:
Xin Cheng, Rui Pan, Junze Tang, Kun Yu, Hailiang Zhang, Xiaoyu Zhao
摘要
肝癌与发病率和死亡率显着相关。低强度超声与纳米医学递送系统的组合有望作为治疗肝癌的替代方案。这项研究的重点是利用叶酸（FA）修饰的纳米颗粒，这些纳米颗粒装有荧光染料DIR和液态氟化合物（PFP）。这些纳米颗粒具有在超声刺激和未来在体内的未来应用下靶向肝癌的潜力。对叶酸酸化的克里巴宁聚乙烯甘油 - 乙二醇二酰基酸酸共聚物共聚物纳米粒子（FA-CRE@PEG-PEG-PLGA NPS）的药代动力学和组织分布进行了分布。评估了药代动力学参数，肝靶向和体内分布。此外，研究了FA-CRE@PEG-PLGA NP与超声辐照对小鼠肝癌H22细胞增殖和急性毒性结合的抑制作用。 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,并且肝靶向效果被明显。此外，体内急性毒性测试表明，FA-CRE@PEG-PLGA NP的不良反应最少，并且可以实现减弱该药物的目的。 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通过超声技术与纳米医学输送系统的结合，肝癌。
Abstract
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.