Designed nanocage displaying ligand-specific peptide bunches for high affinity and biological activity

Jae Og Jeon, Soyoun Kim, Eunsu Choi, Kihyuk Shin, Kiweon Cha, In Seop So, Sun Ji Kim, Eunsung Jun, Dohee Kim, Hyung Jun Ahn, Byung Heon Lee, Seung Hyo Lee, In-San Kim

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Protein-cage nanoparticles are promising multifunctional platforms for targeted delivery of imaging and therapeutic agents owing to their biocompatibility, biodegradability, and low toxicity. The major advantage of protein-cage nanoparticles is the ability to decorate their surfaces with multiple functionalities through genetic and chemical modification to achieve desired properties for therapeutic and/or diagnostic purposes. Specific peptides identified by phage display can be genetically fused onto the surface of cage proteins to promote the association of nanoparticles with a particular cell type or tissue. Upon symmetrical assembly of the cage, peptides are clustered on the surface of the cage protein in bunches. The resulting PBNC (peptide bunches on nanocage) offers the potential of synergistically increasing the avidity of the peptide ligands, thereby enhancing their blocking ability for therapeutic purposes. Here, we demonstrated a proof-of-principle of PBNCs, fusing the interleukin-4 receptor (IL-4R)-targeting peptide, AP-1, identified previously by phage display, with ferritin-L-chain (FTL), which undergoes 24-subunit assembly to form highly stable AP-1-containing nanocage proteins (AP1-PBNCs). AP1-PBNCs bound specifically to the IL-4R-expressing cell line, A549, and their binding and internalization were specifically blocked by anti-IL-4R antibody. AP1-PBNCs exhibited dramatically enhanced binding avidity to IL-4R compared with AP-1 peptide, measured by surface plasmon resonance spectroscopy. Furthermore, treatment with AP1-PBNCs in a murine model of experimental asthma diminished airway hyper-responsiveness and eosinophilic airway inflammation along with decreased mucus hyperproduction. These findings hold great promise for the application of various PBNCs with ligand-specific peptides in therapeutics for different diseases, such as cancer.

Original languageEnglish
Pages (from-to)7462-7471
Number of pages10
JournalACS Nano
Volume7
Issue number9
DOIs
Publication statusPublished - 2013 Sep 24
Externally publishedYes

Fingerprint

activity (biology)
Bioactivity
Peptides
peptides
affinity
Interleukin-4 Receptors
interleukins
Ligands
ligands
proteins
Proteins
Transcription Factor AP-1
Bacteriophages
Nanoparticles
nanoparticles
assembly
Display devices
asthma
mucus
Apoferritins

Keywords

  • AP-1 peptide
  • asthma
  • IL-4 receptor
  • nanoparticles
  • protein cage

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Designed nanocage displaying ligand-specific peptide bunches for high affinity and biological activity. / Jeon, Jae Og; Kim, Soyoun; Choi, Eunsu; Shin, Kihyuk; Cha, Kiweon; So, In Seop; Kim, Sun Ji; Jun, Eunsung; Kim, Dohee; Ahn, Hyung Jun; Lee, Byung Heon; Lee, Seung Hyo; Kim, In-San.

In: ACS Nano, Vol. 7, No. 9, 24.09.2013, p. 7462-7471.

Research output: Contribution to journalArticle

Jeon, JO, Kim, S, Choi, E, Shin, K, Cha, K, So, IS, Kim, SJ, Jun, E, Kim, D, Ahn, HJ, Lee, BH, Lee, SH & Kim, I-S 2013, 'Designed nanocage displaying ligand-specific peptide bunches for high affinity and biological activity', ACS Nano, vol. 7, no. 9, pp. 7462-7471. https://doi.org/10.1021/nn403184u
Jeon, Jae Og ; Kim, Soyoun ; Choi, Eunsu ; Shin, Kihyuk ; Cha, Kiweon ; So, In Seop ; Kim, Sun Ji ; Jun, Eunsung ; Kim, Dohee ; Ahn, Hyung Jun ; Lee, Byung Heon ; Lee, Seung Hyo ; Kim, In-San. / Designed nanocage displaying ligand-specific peptide bunches for high affinity and biological activity. In: ACS Nano. 2013 ; Vol. 7, No. 9. pp. 7462-7471.
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