Multifunctional synthetic nano-chaperone for peptide folding and intracellular delivery

Il-Soo Park, Seongchan Kim, Yeajee Yim, Ginam Park, Jinahn Choi, Cheolhee Won and Dal-Hee Min ()
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Il-Soo Park: Seoul National University
Seongchan Kim: Korea Institute of Science and Technology (KIST)
Yeajee Yim: Seoul National University
Ginam Park: Seoul National University
Jinahn Choi: Seoul National University
Cheolhee Won: Institute of Biotherapeutics Convergence Technology, Lemonex Inc
Dal-Hee Min: Seoul National University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Artificial, synthetic chaperones have attracted much attention in biomedical research due to their ability to control the folding of proteins and peptides. Here, we report bio-inspired multifunctional porous nanoparticles to modulate proper folding and intracellular delivery of therapeutic α-helical peptide. The Synthetic Nano-Chaperone for Peptide (SNCP) based on porous nanoparticles provides an internal hydrophobic environment which contributes in stabilizing secondary structure of encapsulated α-helical peptides due to the hydrophobic internal environments. In addition, SNCP with optimized inner surface modification not only improves thermal stability for α-helical peptide but also supports the peptide stapling methods in situ, serving as a nanoreactor. Then, SNCP subsequently delivers the stabilized therapeutic α-helical peptides into cancer cells, resulting in high therapeutic efficacy. SNCP improves cellular uptake and bioavailability of the anti-cancer peptide, so the cancer growth is effectively inhibited in vivo. These data indicate that the bio-inspired SNCP system combining nanoreactor and delivery carrier could provide a strategy to expedite the development of peptide therapeutics by overcoming existing drawbacks of α-helical peptides as drug candidates.

Date: 2022
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DOI: 10.1038/s41467-022-32268-2

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