Abstract
The relatively low success rate of cancer nanomedicines has raised debate on the roles of the enhanced permeability and retention (EPR) effect in enhancing drug delivery to tumors and improving therapeutic efficacy. In this review, we highlight new strategies beyond the EPR effect for enhancing nanoparticle delivery to tumors. We discuss the roles of transcellular extravasation, receptor-mediated pathways, and protein corona interactions on nanoparticle deposition in tumors. We summarize recent progress in platinum-based combination nanomedicines containing multiple chemotherapeutics with synergistic anticancer mechanisms and multiple anticancer therapies with novel mechanisms to enhance drug delivery and antitumor activities. We also highlight future opportunities in platinum-based combination nanomedicines and key hurdles for the translation of these combination nanomedicines into the clinic.