Document Detail

A Designed Nanocage Displaying Ligand-Specific Peptide Bunches for High Affinity and Biological Activity.
MedLine Citation:
PMID:  23927443     Owner:  NLM     Status:  Publisher    
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 synergistic increasing the avidity of the peptide ligands, thereby enhancing their blocking ability for therapeutic purposes. Here, we demonstrated 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-PBNC). 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 that various PBNCs containing ligand specific peptides could be applied for therapeutics indifferent diseases, such as cancer.
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-8-8
Journal Detail:
Title:  ACS nano     Volume:  -     ISSN:  1936-086X     ISO Abbreviation:  ACS Nano     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-8-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101313589     Medline TA:  ACS Nano     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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