Revisiting the outstanding questions in cancer nanomedicine with a future outlook.

The field of cancer nanomedicine has been fueled by the expectation of mitigating the inefficiencies and life-threatening side effects of conventional chemotherapy. Nanomedicine proposes to utilize the unique nanoscale properties of nanoparticles to address the most pressing questions in cancer treatment and diagnosis. The approval of nano-based products in the 1990s inspired scientific explorations in this direction. However, despite significant progress in the understanding of nanoscale properties, there are only very few success stories in terms of substantial increase in clinical efficacy and overall patient survival. All existing paradigms such as the concept of enhanced permeability and retention (EPR), the stealth effect and immunocompatibility of nanomedicine have been questioned in recent times. In this review we critically examine impediments posed by biological factors to the clinical success of nanomedicine. We put forth current observations on critical outstanding questions in nanomedicine. We also provide the promising side of cancer nanomedicine as we move forward in nanomedicine research. This would provide a future direction for research in nanomedicine and inspire ongoing investigations.