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

TitleA peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries.
Publication TypeJournal Article
Year of Publication2016
AuthorsMann AP, Scodeller P, Hussain S, Joo J, Kwon E, Braun GB, Mölder T, She Z-G, Kotamraju VRamana, Ranscht B, Krajewski S, Teesalu T, Bhatia S, Sailor MJ, Ruoslahti E
JournalNat Commun
Volume7
Pagination11980
Date Published2016
ISSN2041-1723
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.

DOI10.1038/ncomms11980
Alternate JournalNat Commun
PubMed ID27351915