Multifunctional synthetic nano-chaperone for peptide folding and intracellular delivery

• Published in: Nature communications 2022-08, Vol.13 (1), p.4568-4568, Article 4568
• Main Authors: Park, Il-Soo, Kim, Seongchan, Yim, Yeajee, Park, Ginam, Choi, Jinahn, Won, Cheolhee, Min, Dal-Hee
• Format: Article
• Language: English
• Subjects: 14/63; 147/143; 631/61/2298; 639/638/92/152; 639/638/92/611; 639/925/350/354; Bioavailability; Biomedical materials; Cancer; Chaperones; Coils; Drug development; Folding; Humanities and Social Sciences; Hydrophobicity; Intracellular; Medical research; multidisciplinary; Nanoparticles; Peptides; Protein folding; Protein structure; Proteins; Random coil; Science; Science (multidisciplinary); Secondary structure; Surface stability; Thermal stability; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32268-2

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 S ynthetic N ano- C haperone for P eptide (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. Molecular chaperones play an important part in protein folding and delivery in nature. Here, the authors report on the creation of a synthetic chaperone to control the folding of therapeutic peptides from random coil to alpha helix and demonstrate enhanced therapeutic potential in an in vivo tumour model.