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- Publisher Website: 10.1016/j.biomaterials.2018.08.064
- Scopus: eid_2-s2.0-85053129515
- PMID: 30195802
- WOS: WOS:000447569600003
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Article: A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma
Title | A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma |
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Authors | |
Keywords | Polyethylenimine Galactose Liver target IL15 Immunogene therapy |
Issue Date | 2018 |
Publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/biomaterials |
Citation | Biomaterials, 2018, v. 184, p. 20-30 How to Cite? |
Abstract | Successful immunogene therapy depends not only on the therapeutic gene but also on the gene delivery vector. In this study, we synthesized a novel copolymer consisting of low-molecular-weight polyethylenimine (PEI) cross-linked by myo-inositol (INO) and conjugated with a galactose-grafted PEG chain, named LA-PegPI. We characterized the chemical structure and molecular weight of the copolymer and particle properties of LA-PegPI/pDNA. Furthermore, we showed that LA-PegPI/pDNA polyplexes possessed excellent stability in physiological salt solution, low cytotoxicity, and high transfection efficiency in the asialoglycoprotein receptor (ASGPR)-positive liver cells in vitro. Importantly, we also showed that through intraperitoneal injection of LA-PegPI/pDNA nanoparticles, the reporter gene was forcefully expressed in the liver hepatocytes of mice. Finally, we documented that intraperitoneal injection of LA-PegPI/pIL15 nanoparticles effectively suppressed tumor growth and prolonged survival time of tumor-bearing mice via activation of CD8+ T cells and NK cells and upregulation of the cytokines IFN-γ, TNF, and IL12 in an orthotopic hepatocellular carcinoma mouse model. Interestingly, LA-PegPI/pluc nanoparticles could effectively stimulate the proliferation of NK cells and inhibit tumor growth in this model. In summary, LA-PegPI is a useful gene vector for immunogene therapy of hepatocellular carcinoma, and its potential for clinical application warrants further study. |
Persistent Identifier | http://hdl.handle.net/10722/276212 |
ISSN | 2023 Impact Factor: 12.8 2023 SCImago Journal Rankings: 3.016 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Liu, L | - |
dc.contributor.author | Zong, ZM | - |
dc.contributor.author | Liu, Q | - |
dc.contributor.author | Jiang, SS | - |
dc.contributor.author | Zhang, Q | - |
dc.contributor.author | Cen, LQ | - |
dc.contributor.author | Gao, J | - |
dc.contributor.author | Gao, XG | - |
dc.contributor.author | Huang, JD | - |
dc.contributor.author | Liu, Y | - |
dc.contributor.author | Yao, H | - |
dc.date.accessioned | 2019-09-10T02:58:15Z | - |
dc.date.available | 2019-09-10T02:58:15Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | Biomaterials, 2018, v. 184, p. 20-30 | - |
dc.identifier.issn | 0142-9612 | - |
dc.identifier.uri | http://hdl.handle.net/10722/276212 | - |
dc.description.abstract | Successful immunogene therapy depends not only on the therapeutic gene but also on the gene delivery vector. In this study, we synthesized a novel copolymer consisting of low-molecular-weight polyethylenimine (PEI) cross-linked by myo-inositol (INO) and conjugated with a galactose-grafted PEG chain, named LA-PegPI. We characterized the chemical structure and molecular weight of the copolymer and particle properties of LA-PegPI/pDNA. Furthermore, we showed that LA-PegPI/pDNA polyplexes possessed excellent stability in physiological salt solution, low cytotoxicity, and high transfection efficiency in the asialoglycoprotein receptor (ASGPR)-positive liver cells in vitro. Importantly, we also showed that through intraperitoneal injection of LA-PegPI/pDNA nanoparticles, the reporter gene was forcefully expressed in the liver hepatocytes of mice. Finally, we documented that intraperitoneal injection of LA-PegPI/pIL15 nanoparticles effectively suppressed tumor growth and prolonged survival time of tumor-bearing mice via activation of CD8+ T cells and NK cells and upregulation of the cytokines IFN-γ, TNF, and IL12 in an orthotopic hepatocellular carcinoma mouse model. Interestingly, LA-PegPI/pluc nanoparticles could effectively stimulate the proliferation of NK cells and inhibit tumor growth in this model. In summary, LA-PegPI is a useful gene vector for immunogene therapy of hepatocellular carcinoma, and its potential for clinical application warrants further study. | - |
dc.language | eng | - |
dc.publisher | Elsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/biomaterials | - |
dc.relation.ispartof | Biomaterials | - |
dc.subject | Polyethylenimine | - |
dc.subject | Galactose | - |
dc.subject | Liver target | - |
dc.subject | IL15 | - |
dc.subject | Immunogene therapy | - |
dc.title | A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma | - |
dc.type | Article | - |
dc.identifier.email | Huang, JD: jdhuang@hku.hk | - |
dc.identifier.authority | Huang, JD=rp00451 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.biomaterials.2018.08.064 | - |
dc.identifier.pmid | 30195802 | - |
dc.identifier.scopus | eid_2-s2.0-85053129515 | - |
dc.identifier.hkuros | 302549 | - |
dc.identifier.volume | 184 | - |
dc.identifier.spage | 20 | - |
dc.identifier.epage | 30 | - |
dc.identifier.isi | WOS:000447569600003 | - |
dc.publisher.place | Netherlands | - |
dc.identifier.issnl | 0142-9612 | - |