Investigating the EPR effect of nanomedicines in human renal tumors via ex vivo perfusion strategy
Investigating the EPR effect of nanomedicines in human renal tumors via ex vivo perfusion strategy
复制标题
DOI：
10.1016/j.nantod.2020.100970
复制
发表时间：
2020-12-01
期刊：
影响因子：
17.4
通讯作者：
Shi, Linqi
中科院分区：
文献类型：
--
作者：
Ding, Yuxun;Xu, Yingjin;Shi, Linqi
由于许多纳米药物的临床翻译失败，人类实体肿瘤的增透性和滞留(EPR)效应正受到越来越多的质疑。在此，我们建立了一种通过X射线计算机断层扫描(CT)实时研究人肾肿瘤EPR效应的体外灌流模型，证明了人实体肿瘤的EPR效应，并将人肿瘤的EPR效应与动物模型的EPR效应进行了关联。出乎意料的是，超过87%的人肾肿瘤表现出相当大的EPR效应，但在不同的患者中表现出显著的多样性和异质性。我们首次发现肾脏肿瘤的EPR效应与肿瘤大小呈正相关，男性患者肿瘤的EPR效应显著高于男性患者。这种体外模型为研究EPR在人类肿瘤中的作用提供了一种有效的策略。我们的研究结果可能为未来抗癌纳米药物的开发提供理论依据。(C)2020爱思唯尔有限公司。保留所有权利。
The enhanced permeability and retention (EPR) effect in human solid tumors is being increasingly questioned due to the failure of many nanomedicines in their clinical translation. Herein, we developed an ex vivo perfusion model for real-time investigation of the EPR effect in human renal tumors via X-ray computed tomography (CT), proving the EPR in human solid tumors and correlating the EPR effect in human tumors with that in animal models. Unexpectedly, more than 87 % of human renal tumors displayed a considerable EPR effect, which yet showed significant diversity and heterogeneity in different patients. For the first time, we unraveled that the EPR effect in renal tumors was positively correlated with the tumor size, and tumors from male patients exhibited a significantly higher EPR effect. This ex vivo model provides an efficient strategy for investigating the EPR effect in human tumors. Our results may provide a theoretical basis for the development of anticancer nanomedicines in the future. (C) 2020 Elsevier Ltd. All rights reserved.