Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery

C. Lin, Cees-Jan Blaauboer, Miguel Mateos timoneda, Martin C. Lok, Mies Steenbergen, Wim E. Hennink, Zhiyuan Zhong, Jan Feijen, Johannes F.J. Engbersen

Research output: Contribution to journalArticleAcademicpeer-review

140 Citations (Scopus)

Abstract

A group of bioreducible poly(amido amine)s containing multiple disulfide linkages in main chain and oligoamines in side chain (SS–PAOAs) were prepared by Michael-type polyaddition of N-tert-butyloxycarbonyl (N-Boc) protected oligoamine to the disulfide-containing cystaminebisacrylamide, followed by deprotection of the Boc-protective groups. These linear polymers show strong DNA condensation capability at low N/P ratios. The chemical structure of oligoamine side chains (i.e. amine type and amino spacer length) in the SS–PAOAs has a distinct effect on their buffer capacity, transfection efficiency and toxicity profile. The SS–PAOAs containing secondary amino functions in the side chain show high buffer capacities and are able to transfect COS-7 cells in vitro at low N/P ratios, with transfection efficiencies similar or even higher than those of 25 kDa branched pEI, along with very low cytotoxicity as determined by XTT assay. Increase of the alkyl spacer from ethylene to propylene between the amino units in side chains results in significant lower transfection and increased toxicity. This study presents detailed factors influencing the relationship between structure and gene delivery properties and may provide helpful insights for the further development of safe and efficient non-viral vectors.
Original languageUndefined
Pages (from-to)166-174
JournalJournal of controlled release
Volume126
Issue number2
DOIs
Publication statusPublished - 2008

Keywords

  • IR-69285
  • METIS-254509

Cite this

Lin, C. ; Blaauboer, Cees-Jan ; Mateos timoneda, Miguel ; Lok, Martin C. ; Steenbergen, Mies ; Hennink, Wim E. ; Zhong, Zhiyuan ; Feijen, Jan ; Engbersen, Johannes F.J. / Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery. In: Journal of controlled release. 2008 ; Vol. 126, No. 2. pp. 166-174.
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abstract = "A group of bioreducible poly(amido amine)s containing multiple disulfide linkages in main chain and oligoamines in side chain (SS–PAOAs) were prepared by Michael-type polyaddition of N-tert-butyloxycarbonyl (N-Boc) protected oligoamine to the disulfide-containing cystaminebisacrylamide, followed by deprotection of the Boc-protective groups. These linear polymers show strong DNA condensation capability at low N/P ratios. The chemical structure of oligoamine side chains (i.e. amine type and amino spacer length) in the SS–PAOAs has a distinct effect on their buffer capacity, transfection efficiency and toxicity profile. The SS–PAOAs containing secondary amino functions in the side chain show high buffer capacities and are able to transfect COS-7 cells in vitro at low N/P ratios, with transfection efficiencies similar or even higher than those of 25 kDa branched pEI, along with very low cytotoxicity as determined by XTT assay. Increase of the alkyl spacer from ethylene to propylene between the amino units in side chains results in significant lower transfection and increased toxicity. This study presents detailed factors influencing the relationship between structure and gene delivery properties and may provide helpful insights for the further development of safe and efficient non-viral vectors.",
keywords = "IR-69285, METIS-254509",
author = "C. Lin and Cees-Jan Blaauboer and {Mateos timoneda}, Miguel and Lok, {Martin C.} and Mies Steenbergen and Hennink, {Wim E.} and Zhiyuan Zhong and Jan Feijen and Engbersen, {Johannes F.J.}",
year = "2008",
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volume = "126",
pages = "166--174",
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Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery. / Lin, C.; Blaauboer, Cees-Jan; Mateos timoneda, Miguel; Lok, Martin C.; Steenbergen, Mies; Hennink, Wim E.; Zhong, Zhiyuan; Feijen, Jan; Engbersen, Johannes F.J.

In: Journal of controlled release, Vol. 126, No. 2, 2008, p. 166-174.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery

AU - Lin, C.

AU - Blaauboer, Cees-Jan

AU - Mateos timoneda, Miguel

AU - Lok, Martin C.

AU - Steenbergen, Mies

AU - Hennink, Wim E.

AU - Zhong, Zhiyuan

AU - Feijen, Jan

AU - Engbersen, Johannes F.J.

PY - 2008

Y1 - 2008

N2 - A group of bioreducible poly(amido amine)s containing multiple disulfide linkages in main chain and oligoamines in side chain (SS–PAOAs) were prepared by Michael-type polyaddition of N-tert-butyloxycarbonyl (N-Boc) protected oligoamine to the disulfide-containing cystaminebisacrylamide, followed by deprotection of the Boc-protective groups. These linear polymers show strong DNA condensation capability at low N/P ratios. The chemical structure of oligoamine side chains (i.e. amine type and amino spacer length) in the SS–PAOAs has a distinct effect on their buffer capacity, transfection efficiency and toxicity profile. The SS–PAOAs containing secondary amino functions in the side chain show high buffer capacities and are able to transfect COS-7 cells in vitro at low N/P ratios, with transfection efficiencies similar or even higher than those of 25 kDa branched pEI, along with very low cytotoxicity as determined by XTT assay. Increase of the alkyl spacer from ethylene to propylene between the amino units in side chains results in significant lower transfection and increased toxicity. This study presents detailed factors influencing the relationship between structure and gene delivery properties and may provide helpful insights for the further development of safe and efficient non-viral vectors.

AB - A group of bioreducible poly(amido amine)s containing multiple disulfide linkages in main chain and oligoamines in side chain (SS–PAOAs) were prepared by Michael-type polyaddition of N-tert-butyloxycarbonyl (N-Boc) protected oligoamine to the disulfide-containing cystaminebisacrylamide, followed by deprotection of the Boc-protective groups. These linear polymers show strong DNA condensation capability at low N/P ratios. The chemical structure of oligoamine side chains (i.e. amine type and amino spacer length) in the SS–PAOAs has a distinct effect on their buffer capacity, transfection efficiency and toxicity profile. The SS–PAOAs containing secondary amino functions in the side chain show high buffer capacities and are able to transfect COS-7 cells in vitro at low N/P ratios, with transfection efficiencies similar or even higher than those of 25 kDa branched pEI, along with very low cytotoxicity as determined by XTT assay. Increase of the alkyl spacer from ethylene to propylene between the amino units in side chains results in significant lower transfection and increased toxicity. This study presents detailed factors influencing the relationship between structure and gene delivery properties and may provide helpful insights for the further development of safe and efficient non-viral vectors.

KW - IR-69285

KW - METIS-254509

U2 - 10.1016/j.jconrel.2007.11.012

DO - 10.1016/j.jconrel.2007.11.012

M3 - Article

VL - 126

SP - 166

EP - 174

JO - Journal of controlled release

JF - Journal of controlled release

SN - 0168-3659

IS - 2

ER -