Despite advances in radiotherapy (RT), complete tumor eradication remains a clinical challenge, largely due to the insufficient activation of non-apoptotic cell death pathways such as ferroptosis and cuproptosis. To address this, we developed a bimetallic nanozyme, CuFe-MOF-TPP, comprising a CuFe-based metal–organic framework conjugated with triphenylphosphine to enhance RT sensitivity through provoking cuproptosis and ferroptosis. CuFe-MOF-TPP targeted to mitochondria, destroying redox balance by peroxidase-, oxidase-, and glutathione oxidase-like activities. These catalytic functions promoted excessive reactive oxygen species generation and glutathione depletion, leading to oxidative stress in mitochondria. This redox imbalance triggered the generation of ferrous ions, which accelerated lipid peroxidation and subsequently augmented ferroptosis. Concurrently, cuproptosis was promoted through copper ions-mediated aggregation of dihydrolipoamide S-acetyltransferase. Notably, the combination of CuFe-MOF-TPP and RT result in potent tumor suppression via the coordinated delivery of metal ions and spatiotemporally regulated catalytic activity. This strategy offers a promising approach for overcoming radioresistance by synergistically amplifying mitochondrial oxidative stress and activating ferroptosis and cuproptosis, with significant translational potential for clinical cancer therapy.

In the past decade, nanozymes - a unique class of nanomaterials with inherent enzyme-mimetic properties - have fascinated researchers, revealing unexpected enzyme-like activity of nanomaterials previously considered biologically inert. In particular, as metal-free catalyst for biological processes, carbon-based nanozymes have grown in popularity due to their exceptional physical and chemical characteristics. So far, a variety of carbon-based nanozymes with various structures such as fullerene, graphene oxide, carbon dot, carbon nanotube, and carbon nanosphere have been reported possessing a wide range of enzyme-like properties. However, the structure-activity relationship of the carbon-based nanozymes have not yet been comprehensively discussed. In this review, we thoroughly examine the recent findings on the structure-activity connection of carbon nanozymes, in an effort to comprehend the underlying mechanism of carbon nanozymes and throw light on the future direction of the systematic design and construction of functionally specific carbon nanozymes. We also will address the broad range of applications of carbon nanozymes from in vitro detection to replacing specific enzymes in living systems.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory injury. Anti-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing PD. However, traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and sustainability. Herein, Cu-doping zeolite imidazolate framework-8 (ZIF-8) nanozyme is designed to simulate Cu/Zn superoxide dismutase (SOD) by biomimetic mineralization. The nanozyme composite is then integrated into thermosensitive hydrogel (poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA)) to form an effective antioxidant system (Cu-ZIF@Hydrogel). The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion, prolonging nanozyme retention time, and modulating antioxidant activity, thus significantly improving the bioavailability of nanozymes. At the cellular and animal levels of PD, we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve cells. Moreover, the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion site. Therefore, the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.

Artificial nanorobot is a type of robots designed for executing complex tasks at nanoscale. The nanorobot system is typically consisted of four systems, including logic control, driving, sensing and functioning. Considering the subtle structure and complex functionality of nanorobot, the manufacture of nanorobots requires designable, controllable and multi-functional nanomaterials. Here, we propose that nanozyme is a promising candidate for fabricating nanorobots due to its unique properties, including flexible designs, controllable enzyme-like activities, and nano-sized physicochemical characters. Nanozymes may participate in one system or even combine several systems of nanorobots. In this review, we summarize the advances on nanozyme-based systems for fabricating nanorobots, and prospect the future directions of nanozyme for constructing nanorobots. We hope that the unique properties of nanozymes will provide novel ideas for designing and fabricating nanorobotics.