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A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries.

Authors :
Mann, Aman P
Mann, Aman P
Scodeller, Pablo
Hussain, Sazid
Joo, Jinmyoung
Kwon, Ester
Braun, Gary B
Mölder, Tarmo
She, Zhi-Gang
Kotamraju, Venkata Ramana
Ranscht, Barbara
Krajewski, Stan
Teesalu, Tambet
Bhatia, Sangeeta
Sailor, Michael J
Ruoslahti, Erkki
Mann, Aman P
Mann, Aman P
Scodeller, Pablo
Hussain, Sazid
Joo, Jinmyoung
Kwon, Ester
Braun, Gary B
Mölder, Tarmo
She, Zhi-Gang
Kotamraju, Venkata Ramana
Ranscht, Barbara
Krajewski, Stan
Teesalu, Tambet
Bhatia, Sangeeta
Sailor, Michael J
Ruoslahti, Erkki
Source :
Nature communications; vol 7, iss 1, 11980; 2041-1723
Publication Year :
2016

Abstract

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

Details

Database :
OAIster
Journal :
Nature communications; vol 7, iss 1, 11980; 2041-1723
Notes :
application/pdf, Nature communications vol 7, iss 1, 11980 2041-1723
Publication Type :
Electronic Resource
Accession number :
edsoai.on1287392482
Document Type :
Electronic Resource