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A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries
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A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries
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Journal Article
A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries
2016
Overview
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.
Accurate treatment of traumatic brain injuries, a leading cause of neurological disability and death in young people, is hampered by poor accumulation of drugs in the brain. Here, the authors describe a tetrapeptide that can efficiently target brain injuries and deliver therapeutic or diagnostic payload.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 14/63
/ 64/60
/ 692/308
/ 96/34
/ Aged
/ Animals
/ Brain
/ Brain Injuries, Traumatic - diagnostic imaging
/ Brain Injuries, Traumatic - therapy
/ Extracellular Matrix - metabolism
/ Humanities and Social Sciences
/ Humans
/ Injuries
/ Male
/ Mice
/ Peptides
/ Phages
/ Science
/ siRNA
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