Lactose-Poly(ethylene Glycol)-Grafted Poly-l-Lysine as Hepatoma Cell-Targeted Gene Carrier
Identifieur interne : 002751 ( Main/Exploration ); précédent : 002750; suivant : 002752Lactose-Poly(ethylene Glycol)-Grafted Poly-l-Lysine as Hepatoma Cell-Targeted Gene Carrier
Auteurs : Young Hun Choi [États-Unis] ; Feng Liu [États-Unis] ; Jong Sang Park [États-Unis] ; Sung Wan Kim [États-Unis]Source :
- Bioconjugate Chemistry [ 1043-1802 ] ; 1998.
Abstract
To investigate the delivery of DNA into cells, lactose-poly(ethylene glycol)-grafted poly-l-lysine (Lac-PEG-PLL) polymers were synthesized as polymeric gene carriers. The new synthetic carriers, varying the substitution ratio of lactose-poly(ethylene glycol) (lactose-PEG), were characterized by NMR spectroscopy and size-exclusion chromatography. Electrophoretic mobility assay confirmed that the new gene carrier makes a complex with plasmid DNA. The attached poly(ethylene glycol) gives better solubility properties to gene/carrier complex. Transfection experiments showed that Lac-PEG-PLL efficiently delivers DNA to a hepatoma cell line in vitro; the best efficiency was achieved at a 1:3 weight ratio of DNA to carrier. As the lactose-PEG substitution content increased up to 30%, the transfection efficiency increased, which demonstrates that the lactose serves as a targeting moiety. No considerable cytotoxicity was observed due to Lac-PEG-PLL or its complex with DNA within the concentration range for this experiment. The use of chloroquine increased transfection efficiency that indicates the involvement of hydrolytic degradation of the system in lysosome. It is likely that plasmid DNA/Lac-PEG-PLL complexes enter the cells through a receptor-mediated endocytosis mechanism. These results show that Lac-PEG-PLL can form a complex with plasmid DNA and serve as an efficient gene delivery carrier with lower cytotoxicity compared to that of poly-l-lysine. Therefore, it is expected that our Lac-PEG-PLL carrier can be used as an in vivo gene delivery vector.
Url:
DOI: 10.1021/bc980017v
Affiliations:
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Cell-Targeted Gene Carrier</title><author><name sortKey="Choi, Young Hun" sort="Choi, Young Hun" uniqKey="Choi Y" first="Young Hun" last="Choi">Young Hun Choi</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Department of Chemistry, Seoul National University, Seoul, Korea, and Center for Controlled ChemicalDelivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah,Biomedical Polymers Research Building, Room 205, Salt Lake City</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Liu, Feng" sort="Liu, Feng" uniqKey="Liu F" first="Feng" last="Liu">Feng Liu</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Department of Chemistry, Seoul National University, Seoul, Korea, and Center for Controlled ChemicalDelivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah,Biomedical Polymers Research Building, Room 205, Salt Lake City</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Park, Jong Sang" sort="Park, Jong Sang" uniqKey="Park J" first="Jong Sang" last="Park">Jong Sang Park</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Department of Chemistry, Seoul National University, Seoul, Korea, and Center for Controlled ChemicalDelivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah,Biomedical Polymers Research Building, Room 205, Salt Lake City</wicri:cityArea></affiliation><affiliation></affiliation></author><author><name sortKey="Kim, Sung Wan" sort="Kim, Sung Wan" uniqKey="Kim S" first="Sung Wan" last="Kim">Sung Wan Kim</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>Department of Chemistry, Seoul National University, Seoul, Korea, and Center for Controlled ChemicalDelivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah,Biomedical Polymers Research Building, Room 205, Salt Lake City</wicri:cityArea></affiliation><affiliation></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Bioconjugate Chemistry</title><title level="j" type="abbrev">Bioconjugate Chem.</title><idno type="ISSN">1043-1802</idno><idno type="eISSN">1520-4812</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published" when="1998-11-16">1998</date><date when="1998-11-16">1998</date><biblScope unit="vol">9</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="708">708</biblScope><biblScope unit="page" to="718">718</biblScope></imprint><idno type="ISSN">1043-1802</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1043-1802</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">To investigate the delivery of DNA into cells, lactose-poly(ethylene glycol)-grafted poly-l-lysine (Lac-PEG-PLL) polymers were synthesized as polymeric gene carriers. The new synthetic carriers, varying the substitution ratio of lactose-poly(ethylene glycol) (lactose-PEG), were characterized by NMR spectroscopy and size-exclusion chromatography. Electrophoretic mobility assay confirmed that the new gene carrier makes a complex with plasmid DNA. The attached poly(ethylene glycol) gives better solubility properties to gene/carrier complex. Transfection experiments showed that Lac-PEG-PLL efficiently delivers DNA to a hepatoma cell line in vitro; the best efficiency was achieved at a 1:3 weight ratio of DNA to carrier. As the lactose-PEG substitution content increased up to 30%, the transfection efficiency increased, which demonstrates that the lactose serves as a targeting moiety. No considerable cytotoxicity was observed due to Lac-PEG-PLL or its complex with DNA within the concentration range for this experiment. The use of chloroquine increased transfection efficiency that indicates the involvement of hydrolytic degradation of the system in lysosome. It is likely that plasmid DNA/Lac-PEG-PLL complexes enter the cells through a receptor-mediated endocytosis mechanism. These results show that Lac-PEG-PLL can form a complex with plasmid DNA and serve as an efficient gene delivery carrier with lower cytotoxicity compared to that of poly-l-lysine. Therefore, it is expected that our Lac-PEG-PLL carrier can be used as an in vivo gene delivery vector.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Utah</li></region></list><tree><country name="États-Unis"><region name="Utah"><name sortKey="Choi, Young Hun" sort="Choi, Young Hun" uniqKey="Choi Y" first="Young Hun" last="Choi">Young Hun Choi</name></region><name sortKey="Kim, Sung Wan" sort="Kim, Sung Wan" uniqKey="Kim S" first="Sung Wan" last="Kim">Sung Wan Kim</name><name sortKey="Liu, Feng" sort="Liu, Feng" uniqKey="Liu F" first="Feng" last="Liu">Feng Liu</name><name sortKey="Park, Jong Sang" sort="Park, Jong Sang" uniqKey="Park J" first="Jong Sang" last="Park">Jong Sang Park</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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