Targeted Delivery of CRISPR/Cas9‐Mediated Cancer Gene Therapy via Liposome‐Templated Hydrogel Nanoparticles

Chen, Zeming; Liu, Fuyao; Chen, Yanke; Liu, Jun; Wang, Xiaoying; Chen, Ann T.; Deng, Gang; Zhang, Hongyi; Liu, Jie; Hong, Zhangyong; Zhou, Jiangbing

doi:10.1002/adfm.201703036

Cited by 297RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryCRISPR and Genetic Engineering

Targeted Delivery of CRISPR/Cas9‐Mediated Cancer Gene Therapy via Liposome‐Templated Hydrogel Nanoparticles

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Chen, Zeming, Liu, Fuyao, Chen, Yanke, Liu, Jun, Wang, Xiaoying, Chen, Ann T., Deng, Gang, Zhang, Hongyi +3 more·2017·Advanced Functional Materials

DOI 10.1002/adfm.201703036PMC PMC5939593

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Abstract

Due to its simplicity, versatility, and high efficiency, the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has emerged as one of the most promising approaches for treatment of a variety of genetic diseases, including human cancers. However, further translation of CRISPR/Cas9 for cancer gene therapy requires development of safe approaches for efficient, highly specific delivery of both Cas9 and single guide RNA to tumors. Here, novel core-shell nanostructure, liposome-templated hydrogel nanoparticles (LHNPs) that are optimized for efficient codelivery of Cas9 protein and nucleic acids is reported. It is demonstrated that, when coupled with the minicircle DNA technology, LHNPs deliver CRISPR/Cas9 with efficiency greater than commercial agent Lipofectamine 2000 in cell culture and can be engineered for targeted inhibition of genes in tumors, including tumors the brain. When CRISPR/Cas9 targeting a model therapeutic gene, polo-like kinase 1 (PLK1), is delivered, LHNPs effectively inhibit tumor growth and improve tumor-bearing mouse survival. The results suggest LHNPs as versatile CRISPR/Cas9-delivery tool that can be adapted for experimentally studying the biology of cancer as well as for clinically translating cancer gene therapy.

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LHNPs loaded with CRISPR/Cas9 targeting plk1 effectively inhibited U87MG tumor growth.
“After loading with CRISPR/Cas9 targeting polo-like kinase 1 (plk1) gene, LHNPs effectively inhibited U87MG tumor growth [119].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [119]

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Authors: Chen, Z., Liu, F., Chen, Y., Liu, J., Wang, X., Chen, A. T., Deng, G., Zhang, H., Liu, J., Hong, Z., & Zhou, J.
Affiliations: Nankai University (CN)
Yale University (US)
Corresponding author: Hong, Zhangyong
Zhou, Jiangbing
ORCID: Chen, Zeming
Liu, Fuyao
Chen, Yanke
Liu, Jun
Deng, Gang
Zhang, Hongyi
Liu, Jie
Hong, Zhangyong
Zhou, Jiangbing
Venue: Advanced Functional Materials
Publisher: Wiley
Published: 2017-10-16
Volume: 27
Issue: 46
ISSN: 1616-301X (ISSN-L)
1616-3028
DOI: 10.1002/adfm.201703036
PMC: PMC5939593
OpenAlex: W2766680713
Cited by: 297
References: 41
Citations by year: 2026: 11 · 2025: 44 · 2024: 26 · 2023: 39 · 2022: 60 · 2021: 37 · 2020: 39 · 2019: 24 · 2018: 16 · 2012: 1
FWCI: 8.83
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Advanced Functional Materials (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (NS095817, NS095147)
American Brain Tumor Association
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, cancer gene therapy, core-shell nanoparticles, nucleic acid delivery, DNA minicircles, single guide RNA, targeted tumor delivery, brain tumors, PLK1, tumor growth inhibition

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Targeted Delivery of CRISPR/Cas9‐Mediated Cancer Gene Therapy via Liposome‐Templated Hydrogel Nanoparticles

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