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Single-Stranded Nucleic Acid Transmembrane Molecular Carriers Based on Positively Charged Helical Foldamers.

Yunpeng GeWencan LiJun TianHao YuZhenzhu WangMing WangZeyuan Dong
Published in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
Transmembrane delivery of biologically active nucleic acids is an important process in cells and has inspired one to develop advanced drug delivery techniques. In this contribution, molecular-level single-stranded nucleic acid transmembrane carriers are reported based on 3.2 nm long Huc's foldamers (A Orn Q 3 Q 3 ) 8 and ( m Q 3 Q 2 ) 8 with linearly and helically aligned positive charges, respectively. These two foldamers not only show very strong DNA affinity via electrostatic interactions but also discriminatively bind single-stranded DNA (ss-DNA) and double-stranded DNA (ds-DNA), corroborating the importance of precise charge arrangement in the electrostatic interactions. More importantly, these two foldamers are capable of efficiently transporting ss-DNA across the lipid membranes, and the ss-DNA transport activity of (A Orn Q 3 Q 3 ) 8 with linearly aligned charges is higher than that of ( m Q 3 Q 2 ) 8 with helically aligned charges. Thus a type of novel single-stranded nucleic acid transmembrane molecular carriers based on positively charged helical foldamers are introduced. Further, effective and enhanced expression in EGFP-mRNA transfection experiments strongly demonstrates the potential of positively charged foldamers for RNA transmembrane transport and therapy.
Keyphrases
  • nucleic acid
  • drug delivery
  • circulating tumor
  • single molecule
  • poor prognosis
  • induced apoptosis
  • cell death
  • oxidative stress
  • mass spectrometry
  • endoplasmic reticulum stress
  • cell cycle arrest