A Dendronized polymer variant that facilitates safe delivery of a Calcium Channel antagonist to the heart

Viola, Helena M. and Shah, Ashay A. and Kretzmann, Jessica A. and Evans, Cameron W. and Norret, Marck and Iyer, K. Swaminathan and Hool, Livia C. (2020) A Dendronized polymer variant that facilitates safe delivery of a Calcium Channel antagonist to the heart. Nanomedicine: Nanotechnology, Biology and Medicine. p. 102264. ISSN 15499634

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Link to published document: http://doi.org/10.1016/j.nano.2020.102264


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 2h 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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: Repository Administrator
Date Deposited: 21 Jul 2020 22:39
Last Modified: 28 Oct 2021 02:27
URI: http://eprints.victorchang.edu.au/id/eprint/1011

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