Thermo‐triggered Release of CRISPR‐Cas9 System by Lipid‐Encapsulated Gold Nanoparticles for Tumor Therapy

Peng Wang(National Center for Nanoscience and Technology), Lingmin Zhang(Guangdong Pharmaceutical University), Wenfu Zheng(National Center for Nanoscience and Technology), Liman Cong(Tohoku University), Zhaorong Guo(Tohoku University), Yangzhouyun Xie(National Center for Nanoscience and Technology), Le Wang(National Center for Nanoscience and Technology), Rongbing Tang(National Center for Nanoscience and Technology), Qiang Feng(National Center for Nanoscience and Technology), Yoh Hamada(Tohoku University), Kohsuke Gonda(Tohoku University), Zhijian Hu(National Center for Nanoscience and Technology), Xiaochun Wu(National Center for Nanoscience and Technology), Xingyu Jiang(Guangdong Pharmaceutical University)
Angewandte Chemie International Edition
December 28, 2017
10.1002/anie.201708689
Cited by 405

Abstract

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.

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