Engineering Research Center of Nano-Geomaterials of the Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, China.
State Key Laboratory of Material Processing and Die and Mould Technology, School of Materials Science and Engineering, Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074, China.
Angew Chem Int Ed Engl. 2019 Apr 1;58(15):5049-5053. doi: 10.1002/anie.201901527. Epub 2019 Mar 8.
Gene therapy has immense potential as a therapeutic approach to serious diseases. However, efficient delivery and real-time tracking of gene therapeutic agents have not been solved well for successful gene-based therapeutics. Herein we present a versatile gene-delivery strategy for efficient and visualized delivery of therapeutic genes into the targeted nucleus. We developed an integrin-targeted, cell-permeable, and nucleocytoplasmic trafficking peptide-conjugated AIEgen named T NCP for the efficient and sequential targeted delivery of an antisense single-stranded DNA oligonucleotide (ASO) and tracking of the delivery process into the nucleus. As compared with T NCP/siRNA-NPs (siRNA functions mainly in the cytoplasm), T NCP/ASO-NPs (ASO functions mainly in the nucleus) exhibited a better interference effect, which further indicates that T NCP is a nucleus-targeting vector. Moreover, T NCP/ASO-NPs showed a favorable tumor-suppressive effect in vivo.
基因治疗作为一种治疗严重疾病的方法具有巨大的潜力。然而，对于成功的基于基因的治疗，高效的基因治疗药物传递和实时跟踪尚未得到很好的解决。在这里，我们提出了一种多功能的基因传递策略，用于将治疗基因高效地可视化递送至靶向细胞核。我们开发了一种整合素靶向、细胞穿透性和核质转运肽偶联的 AIEgen，命名为 T NCP，用于高效和顺序靶向递送达抗义单链 DNA 寡核苷酸 (ASO)，并跟踪递送至细胞核的过程。与 T NCP/siRNA-NPs（siRNA 主要在细胞质中起作用）相比，T NCP/ASO-NPs（ASO 主要在细胞核中起作用）表现出更好的干扰效果，这进一步表明 T NCP 是一种核靶向载体。此外，T NCP/ASO-NPs 在体内表现出良好的肿瘤抑制作用。
