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Peer-reviewedCC BY-NCRSC advances

Amphipathic peptoid transporters for protein and nanoparticle delivery

  • Juhye Shin1
  • Eun-Ji Kim2
  • Minjae Jun1
  • Min Uk Yang1
  • Kok Jia Yi Erica3
  • Jae Young Lee3
  • Jiwon Seo1
  • Jiyoun Lee2
  1. 1Department of Chemistry, Gwangju Institute of Science and Technology Gwangju 61005 Republic of Korea
  2. 2Department of Next-Generation Applied Sciences, School of Biopharmaceutical and Medical Sciences, Sungshin Women's University Seoul 01133 Republic of Korea
  3. 3School of Materials Science and Engineering, Gwangju Institute of Science and Technology Gwangju 61005 Republic of Korea
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Abstract

The development of efficient intracellular delivery vectors requires a precise balance between cellular uptake and minimal cytotoxicity. Here, we describe a series of cationic amphipathic peptoids designed to evaluate how sequence variation controls cell penetration and uptake. The peptoid series showed substantially higher cellular uptake than previously developed peptoid transporters, while subcellular localization varied across the series. Intracellular distribution was influenced by the type and positioning of hydrophobic residues relative to guanidinium-bearing Nbtg residues. Based on their balanced uptake and cytotoxicity profiles, peptoids 1 and 7 were selected for cargo delivery studies. Biotinylated analogs promoted cellular accumulation of FITC-labeled streptavidin, and peptoid-functionalized PLGA nanoparticles showed enhanced cellular uptake and accumulation in 3D tumor spheroids compared with unmodified or octaarginine-modified nanoparticles. We believe that these cell-penetrating amphipathic peptoids have potential for macromolecular cargo delivery and offer additional advantages, such as sequence tunability, synthetic versatility, and proteolytic stability.

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Cite

BibTeXRIS
BibTeX
@article{shin2026amphipathic,
  title = {{Amphipathic peptoid transporters for protein and nanoparticle delivery}},
  author = {Juhye Shin and Eun-Ji Kim and Minjae Jun and Min Uk Yang and Kok Jia Yi Erica and Jae Young Lee and Jiwon Seo and Jiyoun Lee},
  journal = {RSC advances},
  year = {2026},
  month = oct,
  doi = {10.1039/d6ra06745j},
  url = {https://europepmc.org/article/PMC/PMC13660515},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Amphipathic peptoid transporters for protein and nanoparticle delivery
AU  - Juhye Shin
AU  - Eun-Ji Kim
AU  - Minjae Jun
AU  - Min Uk Yang
AU  - Kok Jia Yi Erica
AU  - Jae Young Lee
AU  - Jiwon Seo
AU  - Jiyoun Lee
PY  - 2026
DA  - 2026/10/13
JO  - RSC advances
DO  - 10.1039/d6ra06745j
UR  - https://europepmc.org/article/PMC/PMC13660515
AB  - The development of efficient intracellular delivery vectors requires a precise balance between cellular uptake and minimal cytotoxicity. Here, we describe a series of cationic amphipathic peptoids designed to evaluate how sequence variation controls cell penetration and uptake. The peptoid series showed substantially higher cellular uptake than previously developed peptoid transporters, while subcellular localization varied across the series. Intracellular distribution was influenced by the type and positioning of hydrophobic residues relative to guanidinium-bearing Nbtg residues. Based on their balanced uptake and cytotoxicity profiles, peptoids 1 and 7 were selected for cargo delivery studies. Biotinylated analogs promoted cellular accumulation of FITC-labeled streptavidin, and peptoid-functionalized PLGA nanoparticles showed enhanced cellular uptake and accumulation in 3D tumor spheroids compared with unmodified or octaarginine-modified nanoparticles. We believe that these cell-penetrating amphipathic peptoids have potential for macromolecular cargo delivery and offer additional advantages, such as sequence tunability, synthetic versatility, and proteolytic stability.
SN  - 2046-2069
ER  -