A Peptide for Targeted, Systemic Delivery of Imaging and Therapeutic Compounds into Acute Brain Injuries

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Jun 29

PMID 27351915

Citations 78

Authors

Aman P Mann

Pablo Scodeller

Sazid Hussain

Jinmyoung Joo

Ester Kwon

Gary B Braun

Tarmo Molder

Zhi-Gang She

Venkata Ramana Kotamraju

Barbara Ranscht

Stan Krajewski

Tambet Teesalu

Sangeeta Bhatia

Michael J Sailor

Erkki Ruoslahti

Affiliations

Soon will be listed here.

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.

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