A dendronized polymer variant that facilitates safe delivery of a calcium channel antagonist to the heart.
Animals
Calcium Channel Blockers
/ chemistry
Calcium Channels, L-Type
/ drug effects
Disease Models, Animal
Guinea Pigs
Heart
/ drug effects
Humans
Myocardial Infarction
/ drug therapy
Myocardial Reperfusion Injury
/ drug therapy
Myocytes, Cardiac
/ drug effects
Nanoparticles
/ chemistry
Peptides
/ chemistry
Polymers
/ chemistry
Dendronized polymer
L-type calcium channel
Myocardial injury
Peptide delivery
Therapy
Journal
Nanomedicine : nanotechnology, biology, and medicine
ISSN: 1549-9642
Titre abrégé: Nanomedicine
Pays: United States
ID NLM: 101233142
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
12
02
2020
revised:
29
04
2020
accepted:
02
07
2020
pubmed:
14
7
2020
medline:
8
7
2021
entrez:
14
7
2020
Statut:
ppublish
Résumé
Therapeutic approaches for myocardial ischemia-reperfusion injury (MI) have been ineffective due to limited bioavailability and poor specificity. We have previously shown that a peptide that targets the α-interaction domain of the cardiac L-type calcium channel (AID-peptide) attenuates MI when tethered to transactivator of transcription sequence (TAT) or spherical nanoparticles. However some reservations remain regarding use of these delivery platforms due to the relationship with human immunodeficiency virus, off-target effects and toxicity. Here we investigate the use of linear dendronized polymers (denpols) to deliver AID-peptide as a potential MI therapy using in vitro, ex vivo and in vivo models. Optimized denpol-complexed AID-peptide facilitated in vitro cardiac uptake of AID-peptide, and reduced MI. Maximal in vivo cardiac uptake was achieved within the 2 h therapeutic time window for acute myocardial infarction. Importantly, optimized denpol-complexed AID-peptide was not toxic. This platform may represent an alternative therapeutic approach for the prevention of MI.
Identifiants
pubmed: 32659322
pii: S1549-9634(20)30118-0
doi: 10.1016/j.nano.2020.102264
pii:
doi:
Substances chimiques
Calcium Channel Blockers
0
Calcium Channels, L-Type
0
Peptides
0
Polymers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102264Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.