Novel EPR-enhanced strategies for targeted drug delivery in pancreatic cancer: An update

Pancreatic cancer (PCa) is one of the leading causes of morbidity worldwide, and theranostic approaches are ventured. The vast stroma surrounding PCa cells has been proven to play a pivotal role in tumor growth and invasion, sequestering chemotherapeutic drugs and reducing their delivery to tumor cells. By exploiting the enhanced permeability and retention (EPR) effect, nanotechnology has risen to the top of medical imaging and therapeutic modalities. The EPR effect is now considered a promising approach for delivering drug-loaded nanostructures to tumors. However, its application is limited due to a disordered vascular network and blocked or embolized blood vessels. Desmoplastic tumors have a dense stroma, so the permeability of the particles into the tumor is low, and these tumors are resistant to nanoparticle-based chemotherapy. There are several strategies for improving the EPR effect by modulating tumor blood vessels, angiogenesis, vascular structure, blood flow, and other factors affecting EPR. Furthermore, by modulating tumor vessels using nanostructures (i.e., nanoparticles (NPs), liposomes, micelles, polymers, nano-biomimetics, etc.) for drug delivery, the EPR effect can be significantly improved. This review will focus on the possible uses of nanostructures to deliver therapeutic drugs for PCa imaging and treatment via the EPR-mediated effect.