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 journalArticlepeer-review

8 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 languageEnglish (US)
Pages (from-to)29481-29495
Number of pages15
JournalACS Applied Materials and Interfaces
Volume9
Issue number35
DOIs
StatePublished - Sep 6 2017
Externally publishedYes

Keywords

  • DNA
  • amphiphile
  • mRNA
  • pyridinium
  • siRNA
  • transfection

ASJC Scopus subject areas

  • Materials Science(all)

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