Tailored to the specific tumour microenvironment, which involves acidity and the overproduction of hydrogen peroxide, advanced nanotechnology has been introduced to generate the hydroxyl radical ( OH) primarily for tumour chemodynamic therapy (CDT) through the Fenton and Fenton-like reactions. Numerous studies have investigated the enhancement of CDT efficiency, primarily the increase in the amount of OH generated. Notably, various strategies based on the Fenton reaction have been employed to enhance OH generation, including nanomaterials selection, modulation of the reaction environment, and external energy fields stimulation, which are discussed systematically in this Minireview. Furthermore, the potential challenges and the methods used to facilitate CDT effectiveness are also presented to support this cutting-edge research area.

Several decades of research have identified the specific tumor microenvironment (TME) to develop promising nanotheranostics, such as pH-sensitive imaging, acidity-sensitive starving therapy, and hydrogen peroxide-activated chemotherapy, etc. Herein, a novel TME-mediated nanoplatform employing antiferromagnetic pyrite nanocubes is presented, exploiting the intratumoral, overproduced peroxide for self-enhanced magnetic resonance imaging (MRI) and photothermal therapy (PTT)/chemodynamic therapy (CDT). Through the activation of excessive peroxide in the tumor microenvironment, pyrite can lead to in situ surface oxidation and generate hydroxyl radicals to kill tumor cells (i.e., CDT). The increase of the valence state of surface Fe significantly promotes the performance of MRI accompanied by CDT. Furthermore, the localized heat by photothermal treatment can accelerate the intratumoral Fenton process, enabling a synergetic PTT/CDT. To our best knowledge, this is the first study to use the TME-response valence-variable strategy based on pyrite for developing a synergetic nanotheranostic, which will open up a new dimension for the design of other TME-based anticancer strategies.

With their unique biological effects on tumor microenvironment, catabolites of nanoparticles can make a significant difference for tumor suppression. We report a facile synthesis method of ultrasmall calcium peroxide nanoparticles and demonstrate their rapid decomposition in tumor region. This can trigger a destructive calcium overload process in tumor cells, lead to cell death, and further tissue calcification, which also allows for medical imaging.