title: A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries.
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.
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
authors.forename: Aman P
authors.initials: AP
authors.lastname: Mann
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.|Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Pablo
authors.initials: P
authors.lastname: Scodeller
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.|AivoCode, La Jolla, California 92037, USA.
authors.forename: Sazid
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jinmyoung
authors.identifier: http://orcid.org/0000-0003-1574-9842
authors.initials: J
authors.lastname: Joo
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.|Institute for Medical Engineering and Science, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Ester
authors.initials: E
authors.lastname: Kwon
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Braun
authors.affiliation: Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Tarmo
authors.initials: T
authors.lastname: Mölder
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: She
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Kotamraju
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ranscht
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
authors.forename: Stan
authors.initials: S
authors.lastname: Krajewski
authors.affiliation: Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
authors.forename: Tambet
authors.initials: T
authors.lastname: Teesalu
authors.affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.|Institute for Medical Engineering and Science, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Michael J
authors.identifier: http://orcid.org/0000-0002-4809-9826
authors.initials: MJ
authors.lastname: Sailor
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.|Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D000368:Aged; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000000981:diagnostic imaging / Q000628:therapy*; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D010455:Peptides
chemical_list: D010455:Peptides