Tuning DNA Condensation with Zwitterionic Polyamidoamine (zPAMAM) Dendrimers

Min An; Gulen Yesilbag Tonga; Sean R. Parkin; Vincent M. Rotello; Jason E. DeRouchey

doi:10.1021/acs.macromol.7b01470

Tuning DNA Condensation with Zwitterionic Polyamidoamine (zPAMAM) Dendrimers

Min An, Gulen Yesilbag Tonga, Sean R. Parkin, Vincent M. Rotello, Jason E. DeRouchey

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

8 Scopus citations

Abstract

Cationic dendrimers are promising vectors for nonviral gene therapies due to their well-defined size and chemistry. We have synthesized a series of succinylated fourth generation (G4) PAMAM dendrimers to control the DNA packaging in dendriplexes, allowing us to probe the role of charge on DNA packaging. The self-assembly of DNA induced by these zwitterionic PAMAM (zPAMAM) was investigated using small-angle X-ray scattering (SAXS). We demonstrate that changing the degree of modification in zPAMAM-DNA significantly alters the packing density of the resulting dendriplexes. Salt sensitivities and pH dependence on the inter-DNA spacing were also examined. The swelling and stability to salt are reduced with increasing degree of PAMAM modification. Lowering the pH leads to significantly tighter hexagonal DNA packaging. In combination, these results show zPAMAM is an effective means to modulate nucleic acid packaging in a deterministic manner.

Original language	English
Pages (from-to)	8202-8211
Number of pages	10
Journal	Macromolecules
Volume	50
Issue number	20
DOIs	https://doi.org/10.1021/acs.macromol.7b01470
State	Published - Oct 24 2017

Bibliographical note

Funding Information:
J.E.D. acknowledges financial support from the National Science Foundation (MCB-1453168). J.E.D. and M.A. acknowledges support from the University of Kentucky Research Challenge Trust Fund (RCTF) Fellowship for Biochemistry. V.M.R. acknowledges support from the NIH (GM077173).

Publisher Copyright:
© 2017 American Chemical Society.

ASJC Scopus subject areas

Organic Chemistry
Polymers and Plastics
Inorganic Chemistry
Materials Chemistry

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10.1021/acs.macromol.7b01470

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title = "Tuning DNA Condensation with Zwitterionic Polyamidoamine (zPAMAM) Dendrimers",

abstract = "Cationic dendrimers are promising vectors for nonviral gene therapies due to their well-defined size and chemistry. We have synthesized a series of succinylated fourth generation (G4) PAMAM dendrimers to control the DNA packaging in dendriplexes, allowing us to probe the role of charge on DNA packaging. The self-assembly of DNA induced by these zwitterionic PAMAM (zPAMAM) was investigated using small-angle X-ray scattering (SAXS). We demonstrate that changing the degree of modification in zPAMAM-DNA significantly alters the packing density of the resulting dendriplexes. Salt sensitivities and pH dependence on the inter-DNA spacing were also examined. The swelling and stability to salt are reduced with increasing degree of PAMAM modification. Lowering the pH leads to significantly tighter hexagonal DNA packaging. In combination, these results show zPAMAM is an effective means to modulate nucleic acid packaging in a deterministic manner.",

author = "Min An and {Yesilbag Tonga}, Gulen and Parkin, {Sean R.} and Rotello, {Vincent M.} and DeRouchey, {Jason E.}",

note = "Funding Information: J.E.D. acknowledges financial support from the National Science Foundation (MCB-1453168). J.E.D. and M.A. acknowledges support from the University of Kentucky Research Challenge Trust Fund (RCTF) Fellowship for Biochemistry. V.M.R. acknowledges support from the NIH (GM077173). Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

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AU - Rotello, Vincent M.

AU - DeRouchey, Jason E.

N1 - Funding Information: J.E.D. acknowledges financial support from the National Science Foundation (MCB-1453168). J.E.D. and M.A. acknowledges support from the University of Kentucky Research Challenge Trust Fund (RCTF) Fellowship for Biochemistry. V.M.R. acknowledges support from the NIH (GM077173). Publisher Copyright: © 2017 American Chemical Society.

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Y1 - 2017/10/24

N2 - Cationic dendrimers are promising vectors for nonviral gene therapies due to their well-defined size and chemistry. We have synthesized a series of succinylated fourth generation (G4) PAMAM dendrimers to control the DNA packaging in dendriplexes, allowing us to probe the role of charge on DNA packaging. The self-assembly of DNA induced by these zwitterionic PAMAM (zPAMAM) was investigated using small-angle X-ray scattering (SAXS). We demonstrate that changing the degree of modification in zPAMAM-DNA significantly alters the packing density of the resulting dendriplexes. Salt sensitivities and pH dependence on the inter-DNA spacing were also examined. The swelling and stability to salt are reduced with increasing degree of PAMAM modification. Lowering the pH leads to significantly tighter hexagonal DNA packaging. In combination, these results show zPAMAM is an effective means to modulate nucleic acid packaging in a deterministic manner.

AB - Cationic dendrimers are promising vectors for nonviral gene therapies due to their well-defined size and chemistry. We have synthesized a series of succinylated fourth generation (G4) PAMAM dendrimers to control the DNA packaging in dendriplexes, allowing us to probe the role of charge on DNA packaging. The self-assembly of DNA induced by these zwitterionic PAMAM (zPAMAM) was investigated using small-angle X-ray scattering (SAXS). We demonstrate that changing the degree of modification in zPAMAM-DNA significantly alters the packing density of the resulting dendriplexes. Salt sensitivities and pH dependence on the inter-DNA spacing were also examined. The swelling and stability to salt are reduced with increasing degree of PAMAM modification. Lowering the pH leads to significantly tighter hexagonal DNA packaging. In combination, these results show zPAMAM is an effective means to modulate nucleic acid packaging in a deterministic manner.

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Tuning DNA Condensation with Zwitterionic Polyamidoamine (zPAMAM) Dendrimers

Abstract

Bibliographical note

ASJC Scopus subject areas

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