A dendronized polymer variant that facilitates safe delivery of a calcium channel antagonist to the heart

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number102264
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume29
DOIs
Publication statusPublished - Oct 2020

Fingerprint Dive into the research topics of 'A dendronized polymer variant that facilitates safe delivery of a calcium channel antagonist to the heart'. Together they form a unique fingerprint.

Cite this