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

Aman P. Mann, Pablo Scodeller, Sazid Hussain, Jinmyoung Joo, Ester Kwon, Gary B. Braun, Tarmo Mölder, Zhi-Gang She, Venkata Ramana Kotamraju, Barbara Ranscht, Stan Krajewski, Tambet Teesalu, Sangeeta Bhatia, Michael J. Sailor and Erkki Ruoslahti ()
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Aman P. Mann: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Pablo Scodeller: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Sazid Hussain: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Jinmyoung Joo: University of California, San Diego
Ester Kwon: Broad Institute of Harvard and MIT
Gary B. Braun: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Tarmo Mölder: Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu
Zhi-Gang She: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Venkata Ramana Kotamraju: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Barbara Ranscht: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Stan Krajewski: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Tambet Teesalu: Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu
Sangeeta Bhatia: Broad Institute of Harvard and MIT
Michael J. Sailor: University of California, San Diego
Erkki Ruoslahti: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11980

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