A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries
Author(s)Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Sailor, Michael J.; Ruoslahti, Erkki; Kwon, Ester J; Bhatia, Sangeeta N; ... Show more Show less
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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.
DepartmentInstitute for Medical Engineering and Science; Harvard University--MIT Division of Health Sciences and Technology
Nature Publishing Group
Mann, Aman P. et al. “A Peptide for Targeted, Systemic Delivery of Imaging and Therapeutic Compounds into Acute Brain Injuries.” Nature Communications 7 (2016): 11980. © 2017 Macmillan Publishers Limited
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