An Updated Review on EPR-Based Solid Tumor Targeting Nanocarriers for Cancer Treatment

SIMPLE SUMMARY: One of the important efforts in the treatment of cancers is to achieve targeted drug delivery by nanocarriers to be more effective and reduce adverse effects. However, due to the adverse responses of nanocarriers in clinical trials due to the very weak EPR effects, doubts have been raised in this regard. In this study, an attempt has been made to take a critical look at EPR approaches to enable the convergence of previous papers and the EPR critics to reach an appropriate therapeutic path. Although the effectiveness of EPR is highly variable due to the complex microenvironment of the tumor, there is high hope for cancer treatment by describing new strategies to overcome the challenges of EPR effect. Furthermore, in this paper an attempt was made to provide a reliable path for future to develop cancer therapeutics based on EPR effect. ABSTRACT: The enhanced permeability and retention (EPR) effect in cancer treatment is one of the key mechanisms that enables drug accumulation at the tumor site. However, despite a plethora of virus/inorganic/organic-based nanocarriers designed to rely on the EPR effect to effectively target tumors, most have failed in the clinic. It seems that the non-compliance of research activities with clinical trials, goals unrelated to the EPR effect, and lack of awareness of the impact of solid tumor structure and interactions on the performance of drug nanocarriers have intensified this dissatisfaction. As such, the asymmetric growth and structural complexity of solid tumors, physicochemical properties of drug nanocarriers, EPR analytical combination tools, and EPR description goals should be considered to improve EPR-based cancer therapeutics. This review provides valuable insights into the limitations of the EPR effect in therapeutic efficacy and reports crucial perspectives on how the EPR effect can be modulated to improve the therapeutic effects of nanomedicine.