Role of inorganic nanoparticle degradation in cancer therapy

Nanomaterials are currently widely exploited for their potential in the development of novel cancer therapies, and so far, mainly nanoparticles (NPs) consisting of liposomes and polymers have made their way into the clinic. However, major bottlenecks for the clinical translation of other types of NPs (i.e. inorganic) are the lack of knowledge concerning their long-term distribution in vivo and their potential toxicity. To counter this, various research groups have worked on soluble NPs, such as zinc oxide (ZnO), copper oxide (CuO), and silver (Ag), which tend to dissolve spontaneously into their ionic form, releasing toxic metal ions and leading to reactive oxygen species (ROS) generation when exposed to cellular environments. By fine-tuning the dissolution kinetics of these NPs, it is possible to control the level of ROS production and thus cytotoxicity to selectively destroy tumor tissue. Specifically, cancer cells tend to exhibit a higher basal level of oxidative stress compared to normal cells due to their higher metabolic rates, and therefore, by engineering NPs that generate sufficient ROS that barely exceed toxic thresholds in cancer cells, normal cells will only experience reversible transient damage. This review focuses on the use of these soluble inorganic NPs for selective cancer therapy and on the various in vitro and in vivo studies that have aimed to control the dissolution kinetics of these NPs, either through particle doping or surface modifications.