Thermo‐triggered Release of CRISPR‐Cas9 System by Lipid‐Encapsulated Gold Nanoparticles for Tumor Therapy |
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| Authors: | Dr Peng Wang Dr Lingmin Zhang Prof Wenfu Zheng Dr Liman Cong Zhaorong Guo Yangzhouyun Xie Le Wang Rongbing Tang Qiang Feng Prof Yoh Hamada Prof Kohsuke Gonda Prof Zhijian Hu Prof Xiaochun Wu Prof Xingyu Jiang |
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| Affiliation: | 1. CAS Center for Excellence in Nanoscience, Beijing Engineering Research Center for BioNanotechnology, CAS Key Lab for Biological Effects of Nanomaterials and Nanosafety, National Center for NanoScience and Technology, ZhongGuanCun, Beijing, China;2. Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences and the Third & Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China;3. Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Sendai, Japan;4. University of Chinese Academy of Sciences, Beijing, China |
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| 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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| Keywords: | CRISPR/Cas9 delivery gold nanoparticles lipids photothermal effect tumor therapy |
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