My research interests focus on the novel functions and applications of nanozyme and ferritin in biomedicine. We discovered new functions of H chain ferritin (HFn) and made a big breakthrough in applications of nanozyme combining new features of HFn. Since then, much original and significant progress has been achieved.
Human HFn targeting tumor and traversing BBB: We firstly discovered that human HFn can target and visualize tumor via binding specifically to a tumor targeting marker transferrin receptor 1 (TfR1) (Nature Nanotechnology 2012；PNAS, 2014). Further studies showed that ferritin traverses blood brain barrier and accumulates in the lysosomal compartment of tumor cells after binding to TfR1 (ACS Nano, 2018). Those findings build up a basis for ferritin nanocarriers and nanozymes in new technologies and methods for tumor diagnosis and therapy.
Ferritin as nanocarrier: Combined with the new characteristics of ferritin, Ferritin Drug Carriers were developed, providing a potential nano-drug platform for central nervous system diseases and malignant tumors.
Another method of loading drugs into ferritin relies on its self-assembly ability. Nanobodies will be displayed on the surface of ferritin after its self-assembly, resulting in high affinity and half-life extension (Analytical Chemistry, 2018).
Novel detection methods based on ferritin and nanozyme: Taking advantages of nanozyme activity and magnetism property of iron oxide nanozyme, we developed a novel rapid, highly sensitive, and easy-to-use nanozyme-strip for emergency infectious disease detection. (Biosensor Bioelectronics, 2015).
In addition, we developed a new type of probes for cancer diagnosis based on nanozyme and ferritin. Working with clinicians, we examined 1400 specimens from patients with ten types of cancer and verified that these probes boast high sensitivity and specificity, which are qualified for clinical use (Nature Nanotechnology, 2012).
Improvements, designs and applications of nanozyme: Compared with natural enzymes, nanozyme boasts many advantages but its activity and selectivity need to be improved. To optimize its catalytic activity, we introduced Histidine residues onto the Fe3O4 nanoparticle surface in order to mimic the enzymatic microenvironment of natural peroxidase enzymes. The catalytic efficiency was enormously enhanced (Chemical Communications，2017).
In addition, we designed a nanozyme using nitrogen-doped porous carbon nanospheres which possess four enzyme-like activities (oxidase, peroxidase, catalase and superoxide dismutase). We then introduce ferritin to this multifunctional nanozyme into lysosomes and boost reactive oxygen species (ROS) generation in a tumor-specific manner. In the acidic environment of tumor lysosomes, oxidase and peroxidase activity were specifically activated and the dissolved oxygen and hydrogen peroxide generated in tumor cells were directly converted into ROS, which can directly kill tumor cells. This work provides a new concept of nanozyme-mediated tumor catalytic therapy (Nature Communications, 2018).