Abstract
Every year, cancer accounts for a vast portion of deaths worldwide. Established clinical protocols are based on chemotherapy, which, however, is not tumor-selective and produces a series of unbearable side effects in healthy tissues. As a consequence, multidrug resistance (MDR) can arise causing metastatic progression and disease relapse. Combination therapy has demonstrated limited responses in the treatment of MDR, mainly due to the different pharmacokinetic properties of administered drugs and to tumor heterogeneity, challenges that still need to be solved in a significant percentage of cancer patients. In this perspective, we briefly discuss the most relevant MDR mechanisms leading to therapy failure and we report the most advanced strategies adopted in the nanomedicine field for the design and evaluation of ad hoc nanocarriers. We present some emerging classes of nanocarriers developed to reverse MDR and discuss recent progress evidencing their limits and promises.