Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117585, Singapore, Singapore.
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
Angew Chem Int Ed Engl. 2020 Oct 19;59(43):19168-19174. doi: 10.1002/anie.202006890. Epub 2020 Aug 25.
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 O 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.
开发非阳离子基因载体并实现功能性核酸在细胞质中的高效内体/溶酶体逃逸是基因传递领域面临的两大挑战。本文中，我们展示了自逃逸球形核酸（SNA）的概念，以实现具有足够内体/溶酶体逃逸能力的光控非阳离子基因传递。在该体系中，将 Bcl-2 反义寡核苷酸（OSA）连接到聚集诱导发射（AIE）光敏剂（PS）纳米颗粒表面以形成核壳 SNA。一旦 SNAs 被肿瘤细胞摄取，在光照下，AIE PS 产生的累积 O 会破坏溶酶体结构，促进 OSA 逃逸。体外和体内的突出结果表明，基于 AIE 的核壳 SNA 可以下调抗凋亡蛋白（Bcl-2）并在没有任何转染试剂的情况下诱导肿瘤细胞凋亡。
