Selective Enhancing Blood Flow in Solid Tumor Tissue Is the Key for Achieving Satisfactory Delivery and Therapeutic Outcome of Nanodrugs via the EPR Effect

The enhanced permeability and retention effect (EPR effect) is a crucial phenomenon for understanding the pathophysiological characteristics of blood vasculature and microenvironments in solid tumors. It is also an essential concept for designing anticancer drugs that can be selectively delivered into tumor tissue via the unique extravasation and retention mechanism for macromolecular drugs. As tumor vasculature is highly heterogeneous, the intensities of the EPR effect vary according to the types and locations of solid tumors in different species. However, the EPR effect is universally observed in a broad spectrum of solid tumors in human cancer as well as experimental animal tumor models. The matter is how to utilize the EPR effect for drug design and clinical application. Many hypotheses were proposed and tested to enhance the EPR effect in solid tumors in order to increase the efficacy of drug delivery. However, we should focus on increasing the blood flow in tumors so that more drugs can be perfused and accumulated inside tumor tissue and execute anticancer activities. Angiotensin II co-administration and the approach of intratumor arterial infusion should be considered to achieve selective tumor tissue perfusion for nanodrugs.