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叶酸-壳聚糖-聚乳酸-羟基乙酸共聚物纳米递送系统抗肝癌细胞的体外研究

Folic Acid-Chitosan-PLGA Nano Delivery System Against Liver Cancer Cells: In Vitro Studies.

作者信息

Hosseini Arianaz, Mohammadnejad Javad, Narmani Asghar, Jafari Hanieh

机构信息

Department of Biology, SR.C., Islamic Azad University, Tehran, Iran.

Department of Nanobiotechnology and Biomimetic, School of Life Science Engineering College of interdisciplinary Science and Technology, University of Tehran, Tehran, Iran.

出版信息

J Biochem Mol Toxicol. 2025 Sep;39(9):e70478. doi: 10.1002/jbt.70478.

Abstract

Among cancers, liver cancer is the fourth leading cause of mortality worldwide and drawbacks of conventional approaches could not inhibit this cancer. Thus, an efficient folic acid (FA)-functionalized chitosan (CS)-poly lactic-co-glycolic acid (PLGA) nanocarrier was fabricated for delivery of sodium butyrate (NB) therapeutics to HepG2 liver cancer cells. The fabricated CS-NB-PLGA-FA nanocarrier was characterized by FT-IR, DLS, TEM, and TGA. A size range of 45 nm to 80 nm, surface charge of 4.2 mV, and drug encapsulation of 15.17% were measured for nanocarrier. Controlled (about fivefolds within 2 h) and pH-sensitive drug release manner observed in PBS as well. The MTT assay indicated that CS-NB-PLGA-FA resulted in about 13% cell viability after 24 h of treatment with 400 nM concentrations (IC: 300 nM). The qRT-PCR technique revealed nearly a 7.9- and 5.8-fold increase for Caspase9 and Bax genes while a decrease of about fivefold for the Bcl2 gene after treatment with CS-NB-PLGA-FA. Additionally, about 60% apoptosis was observed for the cells treated with nanocarrier. Remarkable enhancement did indicate for ROS (increase in the catalase and SOD units). These data have demonstrated that CS-NB-PLGA-FA could be a promising candidate against liver cancer.

摘要

在各类癌症中,肝癌是全球第四大致死原因,传统方法的缺点无法抑制这种癌症。因此,制备了一种高效的叶酸(FA)功能化壳聚糖(CS)-聚乳酸-乙醇酸共聚物(PLGA)纳米载体,用于将丁酸钠(NB)疗法递送至HepG2肝癌细胞。通过傅里叶变换红外光谱(FT-IR)、动态光散射(DLS)、透射电子显微镜(TEM)和热重分析(TGA)对制备的CS-NB-PLGA-FA纳米载体进行了表征。测得纳米载体的尺寸范围为45纳米至80纳米,表面电荷为4.2毫伏,药物包封率为15.17%。在磷酸盐缓冲盐水(PBS)中也观察到了可控的(2小时内约为五倍)和pH敏感的药物释放方式。MTT法表明,在400 nM浓度(IC:300 nM)处理24小时后,CS-NB-PLGA-FA导致细胞活力约为13%。定量逆转录聚合酶链反应(qRT-PCR)技术显示,用CS-NB-PLGA-FA处理后,Caspase9和Bax基因分别增加了近7.9倍和5.8倍,而Bcl2基因减少了约五倍。此外,用纳米载体处理的细胞观察到约60%的凋亡。活性氧(ROS,过氧化氢酶和超氧化物歧化酶单位增加)有显著增强。这些数据表明,CS-NB-PLGA-FA可能是一种有前途的抗肝癌候选物。

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