Engineered nanomedicine triggering ROS storms for enhanced cancer therapeutics

Reactive oxygen species (ROS) play a significant role in regulating various signaling pathways and biochemical reactions within cells during their proliferation and differentiation. Nonetheless, when excessive ROS are accumulated within cells, they will cause severe damage to cellular components like DNA, proteins and lipids. With advances in nanotechnology, 'ROS storm' has become a promising multifaceted therapeutic strategy for tumor treatment, whose mechanism mainly lies in inducing a massive ROS surge within tumors via synthesis optimization, the modulation of tumor adaptive responses and overcoming inherent constraints of individual ROS, so as to exceed the fatal threshold, thereby leading to severe oxidative damage. Therefore, in this review, we would like to focus on the specific strategies of engineered nanomaterials for triggering ROS storms in tumor tissues and the resultant effects, which have been primarily described in terms of augmenting substrate supply, inhibiting antioxidant systems, enhancing catalytic efficiency, enriching the diversity of reactive species and intensifying targeting accumulation, respectively. Moreover, the strong potential of combining this strategy with therapies such as immunotherapy has been demonstrated in various studies and constitutes a key focus of our discussion. At the end of the review, the future outlook and the remaining challenges when it comes to clinical application have also been discussed. This review is aimed at providing an overview of previous anti-cancer studies based on ROS storm, and shedding new light on this innovative strategy with fresh perspectives, thereby facilitating advances in cancer nanomedicine.