Oxidation-Responsive Nanoassemblies for Light-Enhanced Gene Therapy.

Oxidation-Responsive Nanoassemblies for Light-Enhanced Gene Therapy.
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用于光增强基因治疗的氧化响应纳米组件。

DOI:
10.1002/smll.201904017
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发表时间:
2019-09
期刊:
影响因子:
13.3
通讯作者:
Fu-Jian Xu
Fu-Jian Xu
中科院分区:
材料科学1区
文献类型:
--
作者:
Na Zhang;Yu Wang;Rui Wu;Chen Xu;Jing-Jun Nie;Nana Zhao;Bingran Yu;Zunjing Liu;Fu-Jian Xu

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微环境响应型超分子组装体由于其在药物控制释放方面的潜在应用而引起了生物医学领域的极大兴趣。在这项研究中,氧化响应性的超分子聚阳离子组件命名为CPA通过基于β-环糊精的聚阳离子和二茂铁官能化的四氨基酞菁锌核的主客体相互作用制备用于核酸递送。活性氧能加速CPA/pDNA复合物的解体,促进复合物中pDNA的释放,有利于后续的转染。在具有高H2O2浓度的A549细胞中证实了转染效率的这种改善。有趣的是,在各种细胞系如HEK 293和4T1中,CPA介导的转染效率在存在或不存在光的情况下也不同。光敏剂在光照下产生的单氧(1 O2)增加了活性氧的含量,加速了CPAs/pDNA复合物的分解。体内外研究进一步证实,经CPAs介导的抑癌基因p53在光照条件下具有较强的抗肿瘤作用。这项工作为设计和制造具有光增强基因转染性能的氧化响应性纳米组装体提供了一种有前途的策略。
Microenvironment-responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, oxidation-responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via the host-guest interaction of β-cyclodextrin based polycations and a ferrocene-functionalized zinc tetraaminophthalocyanine core. The reactive oxygen species (ROS) can accelerate the disassembly of CPA/pDNA complexes, which would facilitate the release of pDNA in the complexes and further benefit the subsequent transfection. Such improvement in transfection efficiency is proved in A549 cells with high H2 O2 concentration. Interestingly, the transfection efficiencies mediated by CPAs are also different in the presence or absence of light in various cell lines such as HEK 293 and 4T1. The single oxygen (1 O2 ), produced by photosensitizers in the core of CPAs under light, increases the ROS amount and accelerates the disassembly of CPAs/pDNA complexes. In vitro and in vivo studies further illustrate that suppressor tumor gene p53 delivered by CPAs exhibits great antitumor effects under illumination. This work provides a promising strategy for the design and fabrication of oxidation-responsive nanoassemblies with light-enhanced gene transfection performance.
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