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

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

  • Nat Commun. 2016 Jun 28:7:11980. doi: 10.1038/ncomms11980.
Aman P Mann 1,  Pablo Scodeller 1 2,  Sazid Hussain 1 3,  Jinmyoung Joo 4,  Ester Kwon 5 6,  Gary B Braun 1,  Tarmo Mölder 2,  Zhi-Gang She 1,  Venkata Ramana Kotamraju 1,  Barbara Ranscht 1,  Stan Krajewski 1,  Tambet Teesalu 2,  Sangeeta Bhatia 5 6,  Michael J Sailor 4,  Erkki Ruoslahti 1 7
Affiliations

Affiliations

  • 1 Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
  • 2 Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
  • 3 AivoCode, La Jolla, California 92037, USA.
  • 4 Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093, USA.
  • 5 Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • 6 Institute for Medical Engineering and Science, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  • 7 Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
PMID: 27351915 DOI: 10.1038/ncomms11980
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.

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