Abstract 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.

中文翻译：

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通过离体灌注策略研究纳米药物在人肾肿瘤中的 EPR 作用

摘要 由于许多纳米药物在临床转化中的失败，人类实体瘤中增强的渗透性和保留 (EPR) 效应越来越受到质疑。在此，我们开发了一种体外灌注模型，用于通过 X 射线计算机断层扫描 (CT) 实时研究人类肾脏肿瘤中的 EPR 效应，证明人类实体瘤中的 EPR 并将人类肿瘤中的 EPR 效应与动物模型。出乎意料的是，超过 87% 的人类肾脏肿瘤表现出相当大的 EPR 效应，但在不同患者中仍表现出显着的多样性和异质性。我们首次阐明肾肿瘤中的 EPR 效应与肿瘤大小呈正相关，男性患者的肿瘤表现出显着更高的 EPR 效应。这种离体模型为研究人类肿瘤中的 EPR 效应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发展提供理论依据。