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

IF 2.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Arianaz Hosseini, Javad Mohammadnejad, Asghar Narmani, Hanieh Jafari
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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 (IC50: 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.

Abstract Image

叶酸-壳聚糖- plga纳米递送系统抗肝癌细胞:体外研究
在癌症中,肝癌是全球第四大死亡原因,传统方法的缺点无法抑制这种癌症。因此,制备了一种叶酸(FA)功能化壳聚糖(CS)-聚乳酸-羟基乙酸(PLGA)纳米载体,用于向HepG2肝癌细胞递送丁酸钠(NB)药物。对制备的CS-NB-PLGA-FA纳米载体进行了FT-IR、DLS、TEM和TGA表征。纳米载体的尺寸范围为45 ~ 80 nm,表面电荷为4.2 mV,药物包封率为15.17%。在PBS中也观察到受控(2 h内约5倍)和ph敏感的药物释放方式。MTT实验表明,CS-NB-PLGA-FA在400 nM浓度(IC50: 300 nM)处理24 h后,细胞存活率约为13%。qRT-PCR技术显示,CS-NB-PLGA-FA治疗后,Caspase9和Bax基因增加了近7.9倍和5.8倍,而Bcl2基因减少了约5倍。此外,纳米载体处理的细胞凋亡率约为60%。ROS(过氧化氢酶和超氧化物歧化酶单位增加)明显增强。这些数据表明CS-NB-PLGA-FA可能是抗肝癌的有希望的候选药物。
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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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