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Adv Mater. 2018 Feb;30(7). doi: 10.1002/adma.201705383. Epub 2018 Jan 8.

Activatable Protein Nanoparticles for Targeted Delivery of Therapeutic Peptides.

Author information

1
Department of Neurosurgery, Yale University, New Haven, CT, 06511, USA.
2
Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, China.
3
Department of Chemical and Environmental Engineering, Yale University, New Haven, CT, 06511, USA.
4
Department of Cell Biology, Yale University School of Medicine, New Haven, CT, 06510, USA.
5
Institute of Biochemistry and Molecular Biology, College of Life Sciences, Beijing Normal University, Beijing, 100875, China.
6
Department of Neurology, Yale University, New Haven, CT, 06510, USA.
7
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
8
Department of Chemistry, Beijing Normal University, Beijing, 100875, China.

Abstract

Clinical translation of therapeutic peptides, particularly those that require penetration of the cell membrane or are cytolytic, is a major challenge. A novel approach based on a complementary mechanism, which has been widely used for guided synthesis of DNA or RNA nanoparticles, for de novo design of activatable protein nanoparticles (APNPs) for targeted delivery of therapeutic peptides is described. APNPs are formed through self-assembly of three independent polypeptides based on pairwise coiled-coil dimerization. They are capable of long circulation in the blood and can be engineered to target diseases. Peptides to be delivered are incorporated into APNPs and released into the disease microenvironment by locally enriched proteases. It is demonstrated that APNPs mediate efficient delivery of NR2B9c, a neuroprotective peptide that functions after cell penetration, and melittin, a cytolytic peptide that perturbs the lipid bilayer, for effective treatment of stroke and cancer, respectively. Due to their robust properties, simple design, and economic costs, APNPs have great potential to serve as a versatile platform for controlled delivery of therapeutic peptides.

KEYWORDS:

breast cancer; nanoparticles; peptides; stroke; targeted delivery

PMID:
29315863
PMCID:
PMC5812013
DOI:
10.1002/adma.201705383
[Indexed for MEDLINE]
Free PMC Article

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