High amounts of abnormal metabolic products are produced during tumor growth and development. For instance, elevated level of hydrogen peroxide (H₂O₂) is often exhibited in solid tumors, which renders tumor cells more resistant to therapeutic treatment. However, if the accumulated H₂O₂can be converted instead for damaging tumor cells, more effective results of tumor therapy may be then expected, with a mindset of ‘Give tumor a taste of its own medicine’. Natural enzymes with peroxidase activity can be used to convert H₂O₂ into toxic reactive oxygen radicals (ROS) which effectively kills tumor cells. However, most natural enzymes are not suitable for in vivo applications due to their sensitivity and low stability in unfavorable environment, which limits their practical applications. To overcome its limitations, enzyme mimics or artificial enzymes have been developed using chemical synthesis, although the catalytic efficiency of traditional enzyme mimics are often not sufficient.

In recent years, nanomaterials with intrinsic enzyme-like properties (Nanozymes) represent a new generation of enzyme mimics which have high activity, stability and low cost, showing great potential in biomedical applications from in vitro detection to in vivo therapy.With nanozymes having multiple different activities, controlling the in vivo performances of nanozymes has become an urgent challenge.

In the paper entitled “In vivo Guiding Nitrogen-doped Carbon Nanozyme for Tumor Catalytic Therapy”, published by Nature Communications on April 12, 2018, Prof. YAN Xiyun from Institute of Biophysics, Chinese Academy of Sciences and Prof. GAO Lizeng from Institute of translational medicine, School of Medicine, Yangzhou University, China, reported a novel tumor catalytic therapy using nanozymes which convert O₂ and H₂O₂ to toxic ROS for tumor destruction. In the early previous studies, they discovered that iron oxide nanoparticles exhibitedintrinsic peroxidase-like activity (Nature Nanotechnology 2007) and encapsulated in ferritin can be used for in vitro tumor diagnosis (Nature Nanotechnology 2012).

In the current work, the authors developed a novel nanozyme using nitrogen-doped porous carbon nanospheres (N-PCNSs) to mimic four enzyme-like activities (oxidase, peroxidase, catalase, superoxide dismutase). They found that these nanozymes were able to regulate intracellular ROS and boost ROS generation by oxidase and peroxidase activities under acidic microenvironment. To utilize the enzymatic performance for tumor therapy, ferritin was introduced to target tumors and deliver N-PCNSs to lysosome for controlling ROS generation. In vivo tests demonstrated that ferritin-N-PCNSs specifically suppress tumors in animal model, indicating that the nanozymes activities are controllable to perform the desired purpose. Meanwhile, ferritinylation ensured the nanozymes’ specificity and delivery to the tumor. This work demonstrates the feasibility of using nanozymes for tumor catalytic therapy.

Importantly, as a nanomaterial, N-PCNSs own excellent biocompatibility. They were biodegradable under physiological conditions. In addition, N-PCNSs can be made at large scale with low cost. These properties make them superior to natural enzymes in biomedical applications.

This work was commented by the Editor of Nature Communications: ‘If decorated with the right surface modifications, nanoparticles can function as Trojan horses, transporting cell death-facilitating compounds to tumour cells. Here, the authors prepare a particle with four enzyme-like activities and show that ferritin can direct nanoparticles to tumour cells.’.

Dr. FAN Kelong from YAN’s group and Dr. Xi Juqun from GAO’s group are the co-first authors in this paper. The research was supported by Jiangsu Specially-Appointed Professor, Young Elite Scientist Sponsorship Program by CAST, National Natural Science Foundation of China, and Key Research Program of Frontier Sciences, CAS.

For full-text, please see:  https://www.nature.com/articles/s41467-018-03903-8 

Contact: YAN Xiyun
Institute of Biophysics, Chinese Academy of Sciences
Beijing 100101, China
Phone: 86-10-64888584
Email: yanxy（AT）ibp.ac.cn