Investigating the EPR effect of nanomedicines in human renal tumors via ex vivo perfusion strategy

Abstract

The EPR effect of 41 renal tumors collected from clinical patients were analyzed via perfusion strategy, correlating the EPR effect in human tumors with that in animal models and confirming that more than 87 % of the examined renal tumors possess the considerable EPR effect, which yet showed significant diversity and heterogeneity in different patients. • An ex vivo perfusion model was developed for real-time investigation of the EPR effect in human renal tumors via X-ray computed tomography (CT). • The EPR in human solid tumors was positively correlated with that in animal models. • Considerable EPR effect was observed in more than 87% of human renal tumors, which showed significant diversity and heterogeneity. 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.