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

Lina Cui; Jessica L. Cohen; Crystal K. Chu; Peter R. Wich; Paul H. Kierstead; Jean Frechet

doi:10.1021/ja305552u

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

Lina Cui, Jessica L. Cohen, Crystal K. Chu, Peter R. Wich, Paul H. Kierstead, Jean Frechet

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

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.

Original language	English (US)
Pages (from-to)	15840-15848
Number of pages	9
Journal	Journal of the American Chemical Society
Volume	134
Issue number	38
DOIs	https://doi.org/10.1021/ja305552u
State	Published - Sep 18 2012

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: 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.

ASJC Scopus subject areas

Biochemistry
Colloid and Surface Chemistry
General Chemistry
Catalysis

Access to Document

10.1021/ja305552u

Cite this

@article{1fbb9c0072d149af95be3f44fa609e36,

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

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. {\textcopyright} 2012 American Chemical Society.",

author = "Lina Cui and Cohen, {Jessica L.} and Chu, {Crystal K.} and Wich, {Peter R.} and Kierstead, {Paul H.} and Jean Frechet",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: 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.",

year = "2012",

month = sep,

day = "18",

doi = "10.1021/ja305552u",

language = "English (US)",

volume = "134",

pages = "15840--15848",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "38",

}

TY - JOUR

T1 - Conjugation chemistry through acetals toward a dextran-based delivery system for controlled release of siRNA

AU - Cui, Lina

AU - Cohen, Jessica L.

AU - Chu, Crystal K.

AU - Wich, Peter R.

AU - Kierstead, Paul H.

AU - Frechet, Jean

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: 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.

PY - 2012/9/18

Y1 - 2012/9/18

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/562333

UR - https://pubs.acs.org/doi/10.1021/ja305552u

UR - http://www.scopus.com/inward/record.url?scp=84866679606&partnerID=8YFLogxK

U2 - 10.1021/ja305552u

DO - 10.1021/ja305552u

M3 - Article

C2 - 22958132

SN - 0002-7863

VL - 134

SP - 15840

EP - 15848

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 38

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this