A Multifunctional Peptide-Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus
A Multifunctional Peptide-Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus
复制标题
多功能肽缀合 AIEgen，用于高效、顺序地将靶向基因递送至细胞核
DOI：
10.1002/anie.201901527
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发表时间：
2019-04-01
影响因子：
16.6
通讯作者：
Xia, Fan
中科院分区：
文献类型：
--
作者：
Cheng, Yong;Sun, Chunli;Xia, Fan
基因治疗作为治疗严重疾病的方法具有巨大的潜力。然而，基因治疗剂的有效递送和实时跟踪对于成功的基于基因的治疗还没有很好地解决。在这里，我们提出了一个通用的基因传递策略，有效和可视化的治疗基因传递到靶向细胞核。我们开发了一种整合素靶向的，细胞可渗透的，核质运输肽缀合的AIEgen，命名为TDNCP，用于高效和顺序靶向递送反义单链DNA寡核苷酸（阿索）并跟踪递送过程进入细胞核。与TDNCP/siRNA-NPs（siRNA主要在细胞质中发挥作用）相比，TDNCP/ASO-NPs（阿索主要在细胞核中发挥作用）具有更好的干扰效果，进一步表明TDNCP是一种细胞核靶向载体。此外，TDNCP/ASO-NPs在体内显示出良好的肿瘤抑制作用。
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 TDNCP 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 TDNCP/siRNA-NPs (siRNA functions mainly in the cytoplasm), TDNCP/ASO-NPs (ASO functions mainly in the nucleus) exhibited a better interference effect, which further indicates that TDNCP is a nucleus-targeting vector. Moreover, TDNCP/ASO-NPs showed a favorable tumor-suppressive effect in vivo.