A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries.
Aman P MannPablo ScodellerSazid HussainJinmyoung JooEster KwonGary B BraunTarmo MölderZhi-Gang SheVenkata Ramana KotamrajuBarbara RanschtStan KrajewskiTambet TeesaluSangeeta BhatiaMichael J SailorErkki RuoslahtiPublished in: Nature communications (2016)
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.
Keyphrases
- brain injury
- traumatic brain injury
- liver failure
- cerebral ischemia
- subarachnoid hemorrhage
- respiratory failure
- drug induced
- resting state
- white matter
- aortic dissection
- cancer therapy
- public health
- healthcare
- functional connectivity
- high resolution
- hepatitis b virus
- mouse model
- pseudomonas aeruginosa
- adipose tissue
- blood brain barrier
- severe traumatic brain injury
- mental health
- smoking cessation
- intensive care unit
- climate change
- room temperature
- human health
- amino acid
- acute respiratory distress syndrome
- health promotion
- high fat diet induced