含叶酸的壳聚糖纳米药物递送系统的体外促凋亡和抗转移潜力。

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/IJBMS.2023.71731.15602
Ali Hussein Wannas Al-Harmooshee, Masoud Homayouni Tabrizi, Nasim Hayati Roodbari
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引用次数: 0

摘要

目的:用叶酸连接壳聚糖分子包覆禾草灵和绿色合成的银纳米粒子,作为受体介导的给药系统,评估其对人卵巢癌(A2780)和上皮样癌(PANC)细胞的促凋亡和抗转移潜力:利用草药生物平台(Bistorta officinalis)合成了银纳米粒子(AgNP),并用Harmalin包埋。含叶酸的壳聚糖纳米颗粒(HA-fCNP)是利用离子凝胶法合成的。通过 DLS、FESEM 和 Zeta 电位分析对 AgNP 和 HA-fCNP 纳米粒子进行了表征。此外,还分别采用傅立叶变换红外光谱和 XRD 方法测定了 HA-fCNP 的化学性质和 AgNPs 的结晶度。分析了 HA-fCNP 对 A2780、PANC 和 HFF 细胞系的细胞毒性。此外,通过分析 BAX-BCL2 和 MMP2-MMP9 基因表达谱,分别研究了 HA-fCNP 的促凋亡和抗转移潜能。AO/PI和流式细胞术测定了A2780细胞的死亡情况:结果:与正常人包皮成纤维细胞(HFF)相比,HA-fCNP 对 A2780 和 PANC 癌细胞株具有明显的选择性细胞毒性作用。随着 hA-fCNP 处理浓度的增加,A2780 细胞中 SubG1 被抑制的细胞增多,BAX 基因表达上调,这表明 hA-fCNP 对 A2780 细胞具有选择性促凋亡活性。此外,随着 HA-fCNP 处理 A2780 细胞的剂量增加,MMP2 和 MMP9 转移基因的表达明显下调,这也证实了 HA-fCNP 的抗转移活性:结论:HA-fCNP 的癌症选择性细胞毒性、凋亡和抗转移特性被认为是抗癌化合物的适当特性。
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In vitro pro-apoptotic and anti-metastatic potentials of harmaline-silver containing folate-linked chitosan nano-drug delivery system.

Objectives: Harmaline and green-synthesized silver nanoparticles were encapsulated by folate-linked chitosan molecules as a receptor-mediated drug delivery system to evaluate its pro-apoptotic and anti-metastatic potentials on human ovarian (A2780) and epithelioid (PANC) cancer cells.

Materials and methods: The Ag nanoparticles (AgNP) were synthesized utilizing an herbal bio-platform (Bistorta officinalis) and embedded with harmalin. The Harmaline-ag containing folate-linked chitosan nanoparticles (HA-fCNP) were synthesized utilizing the ionic gelation method. Both the AgNP and HA-fCNP nanoparticles were characterized by DLS, FESEM, and Zeta potential analysis. Moreover, the chemical properties of HA-fCNP and the crystallinity of AgNPs were determined by applying FTIR and XRD methods, respectively. The HA-fCNP cytotoxicity was analyzed on A2780, PANC, and HFF cell lines. Moreover, pro-apoptotic and anti-metastatic potentials of HA-fCNP were studied by analyzing the BAX-BCL2 and MMP2-MMP9 gene expression profiles, respectively. The A2780 cellular death was determined by AO/PI and flow cytometry methods.

Results: The HA-fCNP significantly exhibited a selective cytotoxic impact on A2780 and PANC cancerous cell lines compared with normal human foreskin fibroblast (HFF) cells. The increased SubG1-arrested A2780 cells and up-regulated BAX gene expression following the increased treatment concentrations of hA-fCNP indicated its selective pro-apoptotic activity on A2780 cells. Also, the notable down-regulated expressions of MMP2 and MMP9 metastatic genes following the increasing doses of HA-fCNP treatment on A2780 cells confirmed its anti-metastatic activity.

Conclusion: The cancer-selective cytotoxicity, apoptotic, and anti-metastatic properties of HA-fCNP are considered the appropriate properties of an anticancer compound.

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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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