Interfacially Engineered Pyridinium Pseudogemini Surfactants as Versatile and Efficient Supramolecular Delivery Systems for DNA, siRNA, and mRNA

Uttam Satyal; Bogdan Draghici; Lisa L. Dragic; Qiangnan Zhang; Kyle W. Norris; Muniswamy Madesh; Eugen Brailoiu; Marc A. Ilies

doi:10.1021/acsami.7b07066

Interfacially Engineered Pyridinium Pseudogemini Surfactants as Versatile and Efficient Supramolecular Delivery Systems for DNA, siRNA, and mRNA

Uttam Satyal, Bogdan Draghici, Lisa L. Dragic, Qiangnan Zhang, Kyle W. Norris, Muniswamy Madesh, Eugen Brailoiu, Marc A. Ilies

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

14 Scopus citations

Abstract

This article presents the synthesis, self-assembly, and biological activity as transfection agents for pDNA, siRNA, and mRNA of novel pyridinium pseudogemini surfactants, interfacially engineered from the most efficient gemini surfactants and lipids generated in our amphiphile research program. Formulation of novel amphiphiles in water revealed supramolecular properties very similar to those of gemini surfactants, despite their lipidlike charge/mass ratio. This dual character was found also to enhance endosomal escape and significantly increase the transfection efficiency. We were also successful in identifying the parameters governing the efficient delivery of pDNA, siRNA, and mRNA, drawing valuable structure-activity and structure-property relationships for each nucleic acid type, and establishing DNA/siRNA/mRNA comparisons. Several supramolecular complexes identified in this study proved to be extremely efficient nucleic acid delivery systems, displaying excellent serum stability and tissue penetration in three-dimensional organoids.

Original language	English (US)
Pages (from-to)	29481-29495
Number of pages	15
Journal	ACS Applied Materials and Interfaces
Volume	9
Issue number	35
DOIs	https://doi.org/10.1021/acsami.7b07066
State	Published - Sep 6 2017
Externally published	Yes

Keywords

DNA
amphiphile
mRNA
pyridinium
siRNA
transfection

ASJC Scopus subject areas

General Materials Science

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10.1021/acsami.7b07066

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title = "Interfacially Engineered Pyridinium Pseudogemini Surfactants as Versatile and Efficient Supramolecular Delivery Systems for DNA, siRNA, and mRNA",

abstract = "This article presents the synthesis, self-assembly, and biological activity as transfection agents for pDNA, siRNA, and mRNA of novel pyridinium pseudogemini surfactants, interfacially engineered from the most efficient gemini surfactants and lipids generated in our amphiphile research program. Formulation of novel amphiphiles in water revealed supramolecular properties very similar to those of gemini surfactants, despite their lipidlike charge/mass ratio. This dual character was found also to enhance endosomal escape and significantly increase the transfection efficiency. We were also successful in identifying the parameters governing the efficient delivery of pDNA, siRNA, and mRNA, drawing valuable structure-activity and structure-property relationships for each nucleic acid type, and establishing DNA/siRNA/mRNA comparisons. Several supramolecular complexes identified in this study proved to be extremely efficient nucleic acid delivery systems, displaying excellent serum stability and tissue penetration in three-dimensional organoids.",

keywords = "DNA, amphiphile, mRNA, pyridinium, siRNA, transfection",

author = "Uttam Satyal and Bogdan Draghici and Dragic, {Lisa L.} and Qiangnan Zhang and Norris, {Kyle W.} and Muniswamy Madesh and Eugen Brailoiu and Ilies, {Marc A.}",

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AU - Satyal, Uttam

AU - Draghici, Bogdan

AU - Dragic, Lisa L.

AU - Zhang, Qiangnan

AU - Norris, Kyle W.

AU - Madesh, Muniswamy

AU - Brailoiu, Eugen

AU - Ilies, Marc A.

PY - 2017/9/6

Y1 - 2017/9/6

N2 - This article presents the synthesis, self-assembly, and biological activity as transfection agents for pDNA, siRNA, and mRNA of novel pyridinium pseudogemini surfactants, interfacially engineered from the most efficient gemini surfactants and lipids generated in our amphiphile research program. Formulation of novel amphiphiles in water revealed supramolecular properties very similar to those of gemini surfactants, despite their lipidlike charge/mass ratio. This dual character was found also to enhance endosomal escape and significantly increase the transfection efficiency. We were also successful in identifying the parameters governing the efficient delivery of pDNA, siRNA, and mRNA, drawing valuable structure-activity and structure-property relationships for each nucleic acid type, and establishing DNA/siRNA/mRNA comparisons. Several supramolecular complexes identified in this study proved to be extremely efficient nucleic acid delivery systems, displaying excellent serum stability and tissue penetration in three-dimensional organoids.

AB - This article presents the synthesis, self-assembly, and biological activity as transfection agents for pDNA, siRNA, and mRNA of novel pyridinium pseudogemini surfactants, interfacially engineered from the most efficient gemini surfactants and lipids generated in our amphiphile research program. Formulation of novel amphiphiles in water revealed supramolecular properties very similar to those of gemini surfactants, despite their lipidlike charge/mass ratio. This dual character was found also to enhance endosomal escape and significantly increase the transfection efficiency. We were also successful in identifying the parameters governing the efficient delivery of pDNA, siRNA, and mRNA, drawing valuable structure-activity and structure-property relationships for each nucleic acid type, and establishing DNA/siRNA/mRNA comparisons. Several supramolecular complexes identified in this study proved to be extremely efficient nucleic acid delivery systems, displaying excellent serum stability and tissue penetration in three-dimensional organoids.

KW - DNA

KW - amphiphile

KW - mRNA

KW - pyridinium

KW - siRNA

KW - transfection

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SN - 1944-8244

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Interfacially Engineered Pyridinium Pseudogemini Surfactants as Versatile and Efficient Supramolecular Delivery Systems for DNA, siRNA, and mRNA

Abstract

Keywords

ASJC Scopus subject areas

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