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

Author

Listed:
  • Aman P. Mann

    (Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute)

  • Pablo Scodeller

    (Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
    Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu)

  • Sazid Hussain

    (Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
    AivoCode)

  • Jinmyoung Joo

    (University of California, San Diego
    Present address: Biomedical Engineering Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.)

  • Ester Kwon

    (Broad Institute of Harvard and MIT
    Institute for Medical Engineering and Science, and Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • 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
    Institute for Medical Engineering and Science, and Howard Hughes Medical Institute, Massachusetts Institute of Technology)

  • Michael J. Sailor

    (University of California, San Diego)

  • Erkki Ruoslahti

    (Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
    Molecular and Developmental Biology, University of California)

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.

Suggested Citation

  • 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, 2016. "A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11980
    DOI: 10.1038/ncomms11980
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