Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury.
Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury.
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肾靶向氧化还原清道夫治疗预防顺铂诱导的急性肾损伤。
DOI：
10.3389/fphar.2021.790913
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发表时间：
2021
影响因子：
5.6
通讯作者：
Heller DA
中科院分区：
文献类型：
--
作者：
Williams RM;Shah J;Mercer E;Tian HS;Thompson V;Cheung JM;Dorso M;Kubala JM;Gudas LJ;de Stanchina E;Jaimes EA;Heller DA
顺铂诱导的急性肾损伤（CI-AKI）是化疗方案的重要并发症。虽然这种病症与显著降低的存活率和增加的经济负担相关，但没有有效治疗CI-AKI的药理学试剂。该疾病的特征是主要由于氧化应激增加而引起的近端肾小管上皮细胞的急性肾小管坏死。我们研究了一种药物递送策略，以改善获批治疗的药代动力学，作为预防性干预，该治疗通常在CI-AKI中不表现出明显的疗效。在先前的工作中，我们开发了一种靶向肾近端肾小管上皮的肾选择性中尺度纳米颗粒（MNP）。在这里，我们发现纳米颗粒靶向CI-AKI小鼠模型中的肾脏，具有显著的损伤。我们评估了装载活性氧清除剂依达拉奉的MNP，目前用于治疗中风和ALS。我们发现依达拉奉负载的MNP具有显著的治疗益处，包括改善肾功能，我们证明这可能是由于依达拉奉特异性递送引起的肾小管上皮细胞损伤和死亡减少。结果表明，肾选择性依达拉奉给药具有预防接受顺铂化疗患者急性肾损伤的潜力。
Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy.
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影响因子：
19.6
作者：
Han SJ;Williams RM;D'Agati V;Jaimes EA;Heller DA;Lee HT
通讯作者：
Lee HT
影响因子：
2.9
作者：
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通讯作者：
Dennen, Paula
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8.8
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通讯作者：
Schurgers, Marie
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作者：
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通讯作者：
Bailly, Christian
影响因子：
14
作者：
Cheng, Jianjun;Teply, Benjamin A.;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.