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Article: A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma

TitleA novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma
Authors
KeywordsPolyethylenimine
Galactose
Liver target
IL15
Immunogene therapy
Issue Date2018
PublisherElsevier 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?
AbstractSuccessful 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 Identifierhttp://hdl.handle.net/10722/276212
ISSN
2017 Impact Factor: 8.806
2015 SCImago Journal Rankings: 3.565
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, L-
dc.contributor.authorZong, ZM-
dc.contributor.authorLiu, Q-
dc.contributor.authorJiang, SS-
dc.contributor.authorZhang, Q-
dc.contributor.authorCen, LQ-
dc.contributor.authorGao, J-
dc.contributor.authorGao, XG-
dc.contributor.authorHuang, JD-
dc.contributor.authorLiu, Y-
dc.contributor.authorYao, H-
dc.date.accessioned2019-09-10T02:58:15Z-
dc.date.available2019-09-10T02:58:15Z-
dc.date.issued2018-
dc.identifier.citationBiomaterials, 2018, v. 184, p. 20-30-
dc.identifier.issn0142-9612-
dc.identifier.urihttp://hdl.handle.net/10722/276212-
dc.description.abstractSuccessful 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.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/biomaterials-
dc.relation.ispartofBiomaterials-
dc.subjectPolyethylenimine-
dc.subjectGalactose-
dc.subjectLiver target-
dc.subjectIL15-
dc.subjectImmunogene therapy-
dc.titleA novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene delivery vector for immunotherapy of hepatocellular carcinoma-
dc.typeArticle-
dc.identifier.emailHuang, JD: jdhuang@hku.hk-
dc.identifier.authorityHuang, JD=rp00451-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.biomaterials.2018.08.064-
dc.identifier.pmid30195802-
dc.identifier.scopuseid_2-s2.0-85053129515-
dc.identifier.hkuros302549-
dc.identifier.volume184-
dc.identifier.spage20-
dc.identifier.epage30-
dc.identifier.isiWOS:000447569600003-
dc.publisher.placeNetherlands-

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