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.

中文翻译：

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脂质包裹的金纳米粒子热触发释放CRISPR-Cas9系统用于肿瘤治疗

CRISPR / Cas9系统是用于基因编辑的强大工具箱。但是，低的传递效率仍然是阻碍其应用的一大障碍。在本文中，我们报告了一种通过多功能媒介物递送Cas9-sgPlk-1质粒（CP）的策略，用于肿瘤治疗。我们通过静电相互作用将TAT肽修饰的Au纳米颗粒（AuNPs / CP，ACP）上的CP缩合，并将ACP上的脂质（DOTAP，DOPE，胆固醇，PEG2000-DSPE）包被脂质形成脂质包封的，AuNPs缩合的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释放到细胞质中。CP可以在TAT指导下进入细胞核，从而有效敲除靶基因（Plk-1）（黑素瘤）的抑制作用，并在体内和体外抑制肿瘤。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的方法，可用于治疗多种疾病。