Conjugation chemistry through acetals toward a dextran-based delivery system for controlled release of siRNA

Handle URI:
http://hdl.handle.net/10754/562333
Title:
Conjugation chemistry through acetals toward a dextran-based delivery system for controlled release of siRNA
Authors:
Cui, Lina; Cohen, Jessica L.; Chu, Crystal K.; Wich, Peter R.; Kierstead, Paul H.; Frechet, Jean ( 0000-0001-6419-0163 )
Abstract:
New conjugation chemistry for polysaccharides, exemplified by dextran, was developed to enable the attachment of therapeutic or other functional moieties to the polysaccharide through cleavable acetal linkages. The acid-lability of the acetal groups allows the release of therapeutics under acidic conditions, such as that of the endocytic compartments of cells, regenerating the original free polysaccharide in the end. The physical and chemical behavior of these acetal groups can be adjusted by modifying their stereoelectronic and steric properties, thereby providing materials with tunable degradation and release rates. We have applied this conjugation chemistry in the development of water-soluble siRNA carriers, namely acetal-linked amino-dextrans, with various amine structures attached through either slow- or fast-degrading acetal linker. The carriers with the best combination of amine moieties and structural composition of acetals showed high in vitro transfection efficiency and low cytotoxicity in the delivery of siRNA. © 2012 American Chemical Society.
KAUST Department:
Chemical Science Program; Physical Sciences and Engineering (PSE) Division
Publisher:
American Chemical Society (ACS)
Journal:
Journal of the American Chemical Society
Issue Date:
26-Sep-2012
DOI:
10.1021/ja305552u
PubMed ID:
22958132
Type:
Article
ISSN:
00027863
Sponsors:
This work was funded through Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract No. HHSN268201000043C), and the Frechet "various donors" gift fund for the support of research in new materials. P. R. Wich gratefully acknowledges the Alexander von Humboldt Foundation (AvH) for funding. We also thank A. Fischer in the UC Berkeley Cell Culture Facility for her help with cell culture preparation.
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; Chemical Science Program

Full metadata record

DC FieldValue Language
dc.contributor.authorCui, Linaen
dc.contributor.authorCohen, Jessica L.en
dc.contributor.authorChu, Crystal K.en
dc.contributor.authorWich, Peter R.en
dc.contributor.authorKierstead, Paul H.en
dc.contributor.authorFrechet, Jeanen
dc.date.accessioned2015-08-03T10:01:16Zen
dc.date.available2015-08-03T10:01:16Zen
dc.date.issued2012-09-26en
dc.identifier.issn00027863en
dc.identifier.pmid22958132en
dc.identifier.doi10.1021/ja305552uen
dc.identifier.urihttp://hdl.handle.net/10754/562333en
dc.description.abstractNew conjugation chemistry for polysaccharides, exemplified by dextran, was developed to enable the attachment of therapeutic or other functional moieties to the polysaccharide through cleavable acetal linkages. The acid-lability of the acetal groups allows the release of therapeutics under acidic conditions, such as that of the endocytic compartments of cells, regenerating the original free polysaccharide in the end. The physical and chemical behavior of these acetal groups can be adjusted by modifying their stereoelectronic and steric properties, thereby providing materials with tunable degradation and release rates. We have applied this conjugation chemistry in the development of water-soluble siRNA carriers, namely acetal-linked amino-dextrans, with various amine structures attached through either slow- or fast-degrading acetal linker. The carriers with the best combination of amine moieties and structural composition of acetals showed high in vitro transfection efficiency and low cytotoxicity in the delivery of siRNA. © 2012 American Chemical Society.en
dc.description.sponsorshipThis work was funded through Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract No. HHSN268201000043C), and the Frechet "various donors" gift fund for the support of research in new materials. P. R. Wich gratefully acknowledges the Alexander von Humboldt Foundation (AvH) for funding. We also thank A. Fischer in the UC Berkeley Cell Culture Facility for her help with cell culture preparation.en
dc.publisherAmerican Chemical Society (ACS)en
dc.titleConjugation chemistry through acetals toward a dextran-based delivery system for controlled release of siRNAen
dc.typeArticleen
dc.contributor.departmentChemical Science Programen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.identifier.journalJournal of the American Chemical Societyen
dc.contributor.institutionCollege of Chemistry, University of California, Berkeley, CA 94720-1460, United Statesen
dc.contributor.institutionMolecular Imaging Program, School of Medicine, Stanford University, Stanford, CA 94305, United Statesen
kaust.authorFrechet, Jeanen

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