Thermo-triggered release of CRISPR-Cas9 system by lipid-encapsulated gold nanoparticles for tumor therapy
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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Wang et al.'s LACP delivery system enabled effective knock-outs of Plk-1 and inhibited the growth of melanoma both in vitro and in vivo.
“This delivery system enabled effective knock-outs of target gene (Plk-1) and inhibited the growth of melanoma both in vitro and in vivo (Fig. 4B) [118].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [118]
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Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities
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- Authors
- Wang, P., Zhang, L., Zheng, W., Cong, L., Guo, Z., Xie, Y., Wang, L., Tang, R., Feng, Q., Hamada, Y., Gonda, K., Hu, Z., Wu, X., & Jiang, X.
- Affiliations
- National Center for Nanoscience and Technology (CN)
- Third Affiliated Hospital of Guangzhou Medical University (CN)
- Tohoku University (JP)
- Corresponding author
- Zheng, Wenfu
- Jiang, Xingyu
- ORCID
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2018-01-15
- Volume
- 57
- Issue
- 6
- Pages
- 1491-1496
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2779247349
- Cited by
- 410
- References
- 27
- Citations by year
- 2026: 19 · 2025: 52 · 2024: 40 · 2023: 43 · 2022: 63 · 2021: 61 · 2020: 64 · 2019: 44 · 2018: 24
- FWCI
- 14.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81361140345,21535001,31470911,81673039)
- Chinese Academy of Sciences (XDA09030305, XDA09030307)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- CRISPR/Cas9 delivery, gold nanoparticles, TAT peptide, melanoma, targeted gene editing, cancer therapy, electrostatic interactions
- MeSH terms
- CRISPR-Associated Protein 9, RNA, Guide, CRISPR-Cas Systems, Polo-Like Kinase 1, Animals, Glutathione, Gold, Humans, Hyperthermia, Induced, Lasers, Lipids, Melanoma, Experimental, Peptide Fragments, Plasmids, Proto-Oncogene Proteins, Apoptosis, Protein Serine-Threonine Kinases, Gene Transfer Techniques, Microscopy, Confocal, Cell Cycle Proteins, Surface Plasmon Resonance, Cell Line, Tumor, Mice, Metal Nanoparticles
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