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Light-Induced Self-Escape of Spherical Nucleic Acid from Endo/Lysosome for Efficient Non-Cationic Gene Delivery.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-07-19 , DOI: 10.1002/anie.202006890
Leilei Shi 1 , Wenbo Wu 1 , Yukun Duan 1 , Li Xu 2 , Yingying Xu 3 , Lidan Hou 4 , Xiangjun Meng 4 , Xinyuan Zhu 2 , Bin Liu 1
Affiliation  

Developing non‐cationic gene carriers and achieving efficient endo/lysosome escape of functional nucleic acids in cytosol are two major challenges faced by the field of gene delivery. Herein, we demonstrate the concept of self‐escape spherical nucleic acid (SNA) to achieve light controlled non‐cationic gene delivery with sufficient endo/lysosome escape capacity. In this system, Bcl‐2 antisense oligonucleotides (OSAs) were conjugated onto the surface of aggregation‐induced emission (AIE) photosensitizer (PS) nanoparticles to form core–shell SNA. Once the SNAs were taken up by tumor cells, and upon light irradiation, the accumulative 1O2 produced by the AIE PSs ruptured the lysosome structure to promote OSA escape. Prominent in vitro and in vivo results revealed that the AIE‐based core–shell SNA could downregulate the anti‐apoptosis protein (Bcl‐2) and induce tumor cell apoptosis without any transfection reagent.

中文翻译:

光诱导的内/溶酶体球形核酸的自我逃逸,以有效地进行非阳离子基因递送。

开发非阳离子基因载体并实现胞质溶胶中功能核酸的有效内/溶酶体逸出是基因传递领域面临的两个主要挑战。本文中,我们演示了自我逃逸球形核酸(SNA)的概念,以实现具有足够的内/溶酶体逃逸能力的光控非阳离子基因传递。在该系统中,将Bcl-2反义寡核苷酸(OSA)偶联到聚集诱导发射(AIE)光敏剂(PS)纳米颗粒的表面上,形成核-壳SNA。一旦SNA被肿瘤细胞吸收,并且在光照射下,累积的1 O 2由AIE PSs产生的蛋白裂解了溶酶体结构,以促进OSA逃逸。出色的体内和体外结果表明,基于AIE的核壳SNA可以在不使用任何转染试剂的情况下下调抗凋亡蛋白(Bcl-2)并诱导肿瘤细胞凋亡。
更新日期:2020-07-19
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