当前位置: X-MOL 学术ACS Macro Lett. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Oncogenic Epidermal Growth Factor Receptor Silencing in Cervical Carcinoma Mediated by Dynamic Sugar-Benzoxaborole Polyplexes
ACS Macro Letters ( IF 5.8 ) Pub Date : 2020-10-06 , DOI: 10.1021/acsmacrolett.0c00599
Diana Diaz-Dussan 1 , Yi-Yang Peng 1 , Piyush Kumar 2 , Ravin Narain 1
Affiliation  

Although, various types of pharmaceuticals have been developed for cervical carcinomas, treatment with these drugs often results in a number of undesirable side effects, toxicity and multidrug resistance. Here, we aimed at modifying the genetic profiling of cancer cells by silencing the expression of the epidermal growth factor receptor (EGFR) gene. We have synthesized two kinds of RAFT-made, biocompatible, and cationic polymers for the encapsulation of silencing RNA (siRNA). This vector has a dual capability: it contains a cationic segment to complex with the siRNA and an omega-end modified with an oxaborole group via thiol–ene click chemistry that responds to the acidic tumor microenvironment. This structural innovation enables this macromolecule to interact with multiple polyplexes and release the siRNA in a mild acidic environment. A strategy that has shown enhanced gene silencing without elevating the cytotoxicity of the system, as determined by Western blot analysis. The success of this approach has afforded further interest in utilizing boron–carbohydrate interaction in the development of nonviral vectors for gene therapy.

中文翻译:

动态糖-苯并恶唑硼酸酯复合物介导的宫颈癌中的致癌表皮生长因子受体沉默。

尽管已经开发了用于宫颈癌的各种类型的药物,但是用这些药物进行治疗经常会导致许多不良副作用,毒性和多药耐药性。在这里,我们旨在通过沉默表皮生长因子受体(EGFR)基因的表达来修饰癌细胞的基因谱。我们已经合成了两种RAFT制得的,生物相容性的和阳离子聚合物,用于沉默RNA(siRNA)的封装。该载体具有双重功能:它包含一个可与siRNA络合的阳离子片段和一个通过硫醇-烯点击化学反应对氧杂硼烷基进行修饰的ω-末端,该化学反应对酸性肿瘤微环境有反应。这种结构创新使该大分子能够与多个多链体相互作用,并在温和的酸性环境中释放siRNA。通过蛋白质印迹分析确定了一种策略,该策略显示了增强的基因沉默而不增加系统的细胞毒性。这种方法的成功为在基因疗法用非病毒载体的开发中利用硼与碳水化合物的相互作用提供了进一步的兴趣。
更新日期:2020-10-21
down
wechat
bug