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.

由于有限的生物利用度和较差的特异性，对心肌缺血-再灌注损伤（MI）的治疗方法无效。先前我们已经表明，当与转录序列（TAT）的反式激活子或球形纳米粒子束缚时，靶向心脏L型钙通道的α相互作用域的肽（AID肽）会减弱MI。然而，由于与人免疫缺陷病毒，脱靶效应和毒性的关系，在使用这些递送平台方面仍存在一些保留意见。在这里，我们研究使用线性树突化聚合物（denpols）使用体外，离体和体内模型将AID肽作为一种潜在的MI治疗方法来使用。优化了优化的Denpol复合AID肽体外心脏吸收AID肽并降低MI。在急性心肌梗塞的2小时治疗时间范围内，达到了最大的体内心脏吸收。重要的是，优化的Denpol复合AID肽无毒。该平台可代表预防MI的替代治疗方法。