Therapeutic targets in the selective killing of cancer cells by nanomaterials.

Cancer is the result of numerous defects in key regulatory proteins and pathways, and targeting them with anticancer agents is associated with severe systemic toxicity. Increased levels of reactive oxygen species (ROS) and compensatory antioxidant levels in cancer cells have emerged as broad spectrum targets for therapeutic interventions. The biochemical features of cancer provide multiple but overlapping opportunities that could be efficiently exploited by the optimally engineered particulate characteristics of nanomaterials (NMs). Altered potentials in membranes of cancer cells as well as in key organelles favor more stable electrochemical interactions with NMs that have an optimum size and surface charge. This preferential interaction of NMs with cancer cell membranes over normal cell membranes could lead to the greater internalization of NMs in cancer cells. Moreover, the low pH in cytoplasmic fluids and organelles of cancer cells could cause the internalized NMs to dissolve differently than they would in normal cells. In addition to differential dissolution, internalized NMs can induce cell death in cancer cells by activating all possible cell death pathways (apoptosis, necroptosis or autophagy) either alone or in a synergistic manner. With their inherent ability to generate ROS and deplete cellular antioxidants, NMs with optimal physicochemical properties might provide fertile ground in the field of anticancer research.