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Chitosan Modification-Enhanced Silencing Effect of Ad5-shPDGF-D Vector in Breast Cancer Cell Line MDA-MB-231
Current Drug Delivery ( IF 2.4 ) Pub Date : 2022-07-27 , DOI: 10.2174/1567201819666220429093821
Ceyda Ekentok-Atıcı 1 , Jülide Akbuğa 2
Affiliation  

Background: Gene therapeutics are being developed to treat metastatic breast tumors, which are mostly resistant to conventional therapies. Targeting platelet-derived growth factor-D (PDGF-D) is a viable approach because it is known to play roles in angiogenesis and tumor growth. The success of gene therapy is largely dependent on delivery vectors, but both viral and nonviral delivery vectors have their disadvantages. Evolving hybrid vectors are being used to overcome those disadvantages. Objectives: In this study, we aimed to prepare a recombinant adenovirus type-5 (Ad5)/chitosan hybrid vector to deliver shPDGF-D in a breast cancer cell line by the noncovalent coating of the Ad5 surface with chitosan, a natural polymer. Methods: The Ad5/chitosan hybrid vector was prepared by the noncovalent coating of the Ad5 surface with different molecular weights (low and high) and different amounts of chitosan (12.5, 25, and 50 μg), and the effect of silencing PDGF-D was investigated in the MDA-MB-231 cell line. Results: In vitro characterization studies showed that the noncovalent chitosan coating increased the size of the Ad5 particle and changed the surface charge from -16.53 mV to slightly neutral. In vitro cell culture studies also showed that the addition of chitosan with both low (73.61%) and high (65.86%) molecular weight increased the PDGF-D silencing efficiency of the Ad5 vector (42.44%) at 48 hours. While low-molecular-weight chitosan had faster effects, high-molecular-weight chitosan provided a more sustained effect in PDGF-D silencing. Conclusion: The results indicate that noncovalent chitosan modification may improve the therapeutic effects of the Ad5 vector, offering the potential for further in vitro and in vivo experiments.

中文翻译:

壳聚糖修饰增强Ad5-shPDGF-D载体对乳腺癌细胞系MDA-MB-231的沉默作用

背景:正在开发基因疗法来治疗转移性乳腺肿瘤,这些肿瘤大多对常规疗法有耐药性。靶向血小板衍生生长因子-D (PDGF-D) 是一种可行的方法,因为已知它在血管生成和肿瘤生长中发挥作用。基因治疗的成功在很大程度上取决于传递载体,但病毒和非病毒传递载体都有其缺点。正在使用进化的杂交载体来克服这些缺点。目的:在这项研究中,我们旨在制备一种重组腺病毒 5 型 (Ad5)/壳聚糖杂交载体,通过用天然聚合物壳聚糖非共价包被 Ad5 表面来在乳腺癌细胞系中递送 shPDGF-D。方法:Ad5/壳聚糖杂交载体通过非共价包被不同分子量(低和高)的Ad5表面和不同量的壳聚糖(12.5、25和50 μg)制备,并研究其沉默PDGF-D的效果在 MDA-MB-231 细胞系中。结果:体外表征研究表明,非共价壳聚糖涂层增加了 Ad5 颗粒的大小,并将表面电荷从 -16.53 mV 变为微中性。体外细胞培养研究还表明,添加低 (73.61%) 和高 (65.86%) 分子量的壳聚糖可提高 Ad5 载体 (42.44%) 在 48 小时时的 PDGF-D 沉默效率。虽然低分子量壳聚糖的作用更快,但高分子量壳聚糖在 PDGF-D 沉默中提供了更持久的作用。结论:
更新日期:2022-07-27
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