Thermo-triggered Release of CRISPR-Cas9 System by Lipid-Encapsulated Gold Nanoparticles for Tumor Therapy
Thermo-triggered Release of CRISPR-Cas9 System by Lipid-Encapsulated Gold Nanoparticles for Tumor Therapy
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脂质封装金纳米颗粒热触发释放 CRISPR-Cas9 系统用于肿瘤治疗
DOI：
10.1002/anie.201708689
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Jiang Xingyu
中科院分区：
文献类型：
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作者：
Wang Peng;Zhang Lingmin;Zheng Wenfu;Cong Liman;Guo Zhaorong;Xie Yangzhouyun;Wang Le;Tang Rongbing;Feng Qiang;Hamada Yoh;Gonda Kohsuke;Hu Zhijian;Wu Xiaochun;Jiang Xingyu
CRISPR/Cas9系统是基因编辑的强大工具箱。然而，低传输效率仍然是阻碍其应用的一大障碍。在本文中，我们报告了通过多功能载体递送Cas9-sgPlk-1质粒（CP）用于肿瘤治疗的策略。我们通过静电相互作用将CP凝聚在达特肽修饰的Au纳米颗粒（AuNPs/CP，ACP）上，并在ACP上涂覆脂质（DOTAP，DOPE，胆固醇，PEG 2000-DSPE）以形成脂质包裹的AuNPs凝聚CP（LACP）。LACP可以通过AuNPs的激光触发热效应进入肿瘤细胞并将CP释放到胞质溶胶中; CP可以通过达特引导进入细胞核，从而在体外和体内有效敲除肿瘤（黑色素瘤）的靶基因（Plk-1）并抑制肿瘤。 这种AuNPs浓缩、脂质封装和激光控制的递送系统为高效CRISPR/Cas9递送和靶向基因编辑提供了一种通用方法，用于治疗各种疾病。
CRISPR/Cas9 system is a powerful toolbox for gene editing. However, the low delivery efficiency is still a big hurdle impeding its applications. Herein, we report a strategy to deliver Cas9‐sgPlk‐1 plasmids (CP) by a multifunctional vehicle for tumor therapy. We condensed CPs on TAT peptide‐modified Au nanoparticles (AuNPs/CP, ACP) via electrostatic interactions, and coated lipids (DOTAP, DOPE, cholesterol, PEG2000‐DSPE) on the ACP to form lipid‐encapsulated, AuNPs‐condensed CP (LACP). LACP can enter tumor cells and release CP into the cytosol by laser‐triggered thermo‐effects of the AuNPs; the CP can enter nuclei by TAT guidance, enabling effective knock‐outs of target gene (Plk‐1) of tumor (melanoma) and inhibition of the tumor both in vitro and in vivo. This AuNPs‐condensed, lipid‐encapsulated, and laser‐controlled delivery system provides a versatile method for high efficiency CRISPR/Cas9 delivery and targeted gene editing for treatment of a wide spectrum of diseases.