Bridging cancer biology and the patients' needs with nanotechnology-based approaches.

Cancer remains as stressful condition and a leading cause of death in the western world. Actual cornerstone treatments of cancer disease rest as an elusive alternative, offering limited efficacy with extensive secondary effects as a result of severe cytotoxic effects in healthy tissues. The advent of nanotechnology brought the promise to revolutionize many fields including oncology, proposing advanced systems for cancer treatment. Drug delivery systems rest among the most successful examples of nanotechnology. Throughout time they have been able to evolve as a function of an increased understanding from cancer biology and the tumor microenvironment. Marketing of Doxil® unleashed a remarkable impulse in the development of drug delivery systems. Since then, several nanocarriers have been introduced, with aspirations to overrule previous technologies, demonstrating increased therapeutic efficacy besides decreased toxicity. Spatial and temporal targeting to cancer cells has been explored, as well as the use of drug combinations co-encapsulated in the same particle as a mean to take advantage of synergistic interactions in vivo. Importantly, targeted delivery of siRNA for gene silencing therapy has made its way to the clinic for a "first in man" trial using lipid-polymeric-based particles. Focusing in state-of-the-art technology, this review will provide an insightful vision on nanotechnology-based strategies for cancer treatment, approaching them from a tumor biology-driven perspective, since their early EPR-based dawn to the ones that have truly the potential to address unmet medical needs in the field of oncology, upon targeting key cell subpopulations from the tumor microenvironment.