Biomimicking Platelet-Monocyte Interactions as a Novel Targeting Strategy for Heart Healing
Biomimicking Platelet-Monocyte Interactions as a Novel Targeting Strategy for Heart Healing
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DOI：
10.1002/adhm.201600724
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发表时间：
2016-10-01
影响因子：
10
通讯作者：
Hsieh, Patrick C. H.
中科院分区：
文献类型：
--
作者：
Cheng, Bill;Toh, Elsie K. W.;Hsieh, Patrick C. H.
在心肌梗死后幸存的患者中，许多人会继续发展为充血性心力衰竭（CHF）。尽管人们不断努力开发梗塞后治疗的新方法，但慢性心力衰竭患者仍然没有有效的治疗选择。目前，心脏保护药物的输送完全依赖于通过发生在梗塞部位附近的增强渗透性和保留（EPR）效应的被动吸收。然而，与癌症不同，在缺血性疾病中，EPR 效应仅在梗塞后短时间内存在，因此不足以提供有意义的心脏保护作用。梗塞后脾单核细胞大量募集到心脏，并且已知在循环过程中与血小板相互作用。因此，策略是通过开发血小板样脂蛋白体（PLP）来利用这种相互作用，仿生血小板与循环单核细胞的相互作用。 PLP 在体外对单核细胞表现出很强的结合亲和力，但对内皮细胞则不然，模仿正常血小板活性。此外，活体多光子成像显示，与普通脂质体相比，PLP 不会聚集在未损伤的内皮上，而是在梗塞后 72 小时聚集在损伤部位。重要的是，PLP 以不依赖于 EPR 的方式增强抗炎药物钴原卟啉对心脏的靶向，从而产生更好的治疗结果。
In patients who survive myocardial infarction, many go on to develop congestive heart failure (CHF). Despite ongoing efforts to develop new approaches for postinfarction therapy, there are still no effective therapeutic options available to CHF patients. Currently, the delivery of cardioprotective drugs relies entirely on passive uptake via the enhanced permeability and retention (EPR) effect which occurs in proximity to the infarction site. However, in ischemic disease, unlike in cancer, the EPR effect only exists for a short duration postinfarction and thus insufficient for meaningful cardioprotection. Splenic monocytes are recruited to the heart in large numbers postinfarction, and are known to interact with platelets during circulation. Therefore, the strategy is to exploit this interaction by developing platelet-like proteoliposomes (PLPs), biomimicking platelet interactions with circulating monocytes. PLPs show strong binding affinity for monocytes but not for endothelial cells in vitro, mimicking normal platelet activity. Furthermore, intravital multiphoton imaging shows that comparing to plain liposomes, PLPs do not aggregate on uninjured endothelium but do accumulate at the injury site 72 h postinfarction. Importantly, PLPs enhance the targeting of anti-inflammatory drug, cobalt protoporphyrin, to the heart in an EPR-independent manner, which result in better therapeutic outcome.