Cysteine-Based Redox-Responsive Nanoparticles for Fibroblast-Targeted Drug Delivery in the Treatment of Myocardial Infarction.
Cysteine-Based Redox-Responsive Nanoparticles for Fibroblast-Targeted Drug Delivery in the Treatment of Myocardial Infarction.
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DOI：
10.1021/acsnano.2c10042
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发表时间：
2023-03
期刊：
影响因子：
17.1
通讯作者：
Xiaoqian Ji;Y. Meng;Qiyuan Wang;Tong Tong-Tong;Zhun Liu;Jianqing Lin;Bin Li;Yan Wei;Xinru You;Yushan Lei;Mingyuan Song;Liying Wang;Yi Guo;Yuexiang Qiu;Zhong-Yan Chen;Bifang Mai;Shuanglun Xie;Jun Wu;Nan Cao
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文献类型：
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作者：
Xiaoqian Ji;Y. Meng;Qiyuan Wang;Tong Tong-Tong;Zhun Liu;Jianqing Lin;Bin Li;Yan Wei;Xinru You;Yushan Lei;Mingyuan Song;Liying Wang;Yi Guo;Yuexiang Qiu;Zhong-Yan Chen;Bifang Mai;Shuanglun Xie;Jun Wu;Nan Cao
心肌梗死（MI）后，激活的心脏成纤维细胞（CF）开始重塑心肌，导致心肌纤维化甚至心力衰竭。目前没有治疗方法可用于预防MI诱导的病理性纤维化的发展。大多数药理学试验因局部药物活性差和全身毒性引起的副作用而失败，这主要是由于缺乏对活化CF具有选择性的心脏靶向药物递送系统。在这里，我们开发了一种还原型谷胱甘肽（GSH）响应性纳米颗粒平台，能够靶向递送药物到MI后心脏梗死区域内的活化CF。与全身给药相比，CF靶向递送PF 543（一种在高通量抗纤维化药物筛选中鉴定的鞘氨醇激酶1抑制剂）在MI小鼠模型中具有更高的疗效和更低的全身毒性。我们的研究结果提供了一个CF靶向策略，提供治疗药物的心脏纤维化的药物干预。
Upon myocardial infarction (MI), activated cardiac fibroblasts (CFs) begin to remodel the myocardium, leading to cardiac fibrosis and even heart failure. No therapeutic approaches are currently available to prevent the development of MI-induced pathological fibrosis. Most pharmacological trials fail from poor local drug activity and side effects caused by systemic toxicity, largely due to the lack of a heart-targeted drug delivery system that is selective for activated CFs. Here, we developed a reduced glutathione (GSH)-responsive nanoparticle platform capable of targeted delivering of drugs to activated CFs within the infarct area of a post-MI heart. Compared with systemic drug administration, CF-targeted delivery of PF543, a sphingosine kinase 1 inhibitor identified in a high-throughput antifibrotic drug screening, had higher therapeutic efficacy and lower systemic toxicity in a MI mouse model. Our results provide a CF-targeted strategy to deliver therapeutic agents for pharmacological intervention of cardiac fibrosis.