Cancer nanomedicine: magic bullets to fight tumors

In the last decades, nanotechnology has been recognised as an innovative and emerging tool for diagnosis and therapy of diseases, due to the ability of nanoscale based materials to drive several compounds in a specific area of the body, thus controlling their fate after administration. On these basis, a growing interest has been devoted to the development of innovative cancer nanomedicines for drug delivery that can be engineered to provide adequate features to overcome the main biological barriers encountered by free anticancer drugs, thus optimizing their pharmacological/toxicological profiles. Several polymeric nanoncologicals have been proposed , some of them nowadays being under preclinical/clinical trials or marketed. Moreover, to implement multimodality of a cancer therapy, co-administration of multiple therapeutic agents (e.g., gene therapy, photothermal therapy, photodynamic therapy and radiotherapy) through multifunctional nanocarriers have been explored to improve therapeutic response and fight tumors through different synergic mechanisms. A possible strategy to home all the drugs selectively in the tumor resides in the design of nanomedicines engineered to be: i) long-circulating once intravenously injected and passively targeted at tumor site through Enhanced Permeability and Retention effect; ii) actively targeted to a specific tumor, through the decoration of their surface with different targeting motifs binding particular receptors overexpressed in cancer cells or blood vessels; iii) selectively sensitive at tumor level to extracellular or intracellular stimuli for "on demand" delivery at a diseased site.
In this context, results obtained from passive, active and stimuli-sensitive polymeric cancer nanomedicines for the delivery of one or more therapeutics (conventional anticancer drugs, siRNA, photosensitizers, NO donors) to tumors will be presented. Fundamental design rules and formulation strategies dictated by the biological barriers as well as the selected administration routes will be described. Finally, indications on their in vitro/in vivo potential in terms of toxicity/activity in different tumor models will be provided.