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Thermo-triggered Release of CRISPR-Cas9 System by Lipid-Encapsulated Gold Nanoparticles for Tumor Therapy.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2018 Feb 05; Vol. 57 (6), pp. 1491-1496. Date of Electronic Publication: 2018 Jan 15. - Publication Year :
- 2018
-
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.<br /> (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Animals
Apoptosis radiation effects
Cell Cycle Proteins genetics
Cell Line, Tumor
Gene Transfer Techniques
Glutathione chemistry
Humans
Hyperthermia, Induced
Lasers
Melanoma, Experimental pathology
Mice
Microscopy, Confocal
Peptide Fragments chemistry
Plasmids genetics
Protein Serine-Threonine Kinases genetics
Proto-Oncogene Proteins genetics
RNA, Guide, CRISPR-Cas Systems genetics
Surface Plasmon Resonance
Polo-Like Kinase 1
CRISPR-Associated Protein 9 genetics
Gold chemistry
Lipids chemistry
Melanoma, Experimental therapy
Metal Nanoparticles chemistry
Plasmids therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 57
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 29282854
- Full Text :
- https://doi.org/10.1002/anie.201708689