TY - JOUR
T1 - Thermo-triggered Release of CRISPR-Cas9 System by Lipid-Encapsulated Gold Nanoparticles for Tumor Therapy
AU - Wang, Peng
AU - Zhang, Lingmin
AU - Zheng, Wenfu
AU - Cong, Liman
AU - Guo, Zhaorong
AU - Xie, Yangzhouyun
AU - Wang, Le
AU - Tang, Rongbing
AU - Feng, Qiang
AU - Hamada, Yoh
AU - Gonda, Kohsuke
AU - Hu, Zhijian
AU - Wu, Xiaochun
AU - Jiang, Xingyu
N1 - Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/2/5
Y1 - 2018/2/5
N2 - 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.
AB - 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.
KW - CRISPR/Cas9 delivery
KW - gold nanoparticles
KW - lipids
KW - photothermal effect
KW - tumor therapy
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U2 - 10.1002/anie.201708689
DO - 10.1002/anie.201708689
M3 - Article
C2 - 29282854
AN - SCOPUS:85040595248
SN - 1433-7851
VL - 57
SP - 1491
EP - 1496
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 6
ER -