EBV is a ubiquitous human herpes virus, which spreads through saliva. Infection is very common and most people become infected with EBV when they were young, but they will not develop any symptoms or symptoms that are not distinguishable from mild childhood illnesses. There is ~ 200,000 EBV-associated cancer new cases per year attributes to EBV. EBV causes both infectious mononucleosis and lymphoproliferative diseases. The oncogenic development of other cancers (e.g. nasopharyngeal cancer (NPC) and a subgroup of EBV-positive gastric cancer) is also associated with the latent infection of EBV. Almost all NPC tumors contain EBV, and the NPC incidence is most common in southern China and Southeast Asia. One of the EBV latent proteins, EBNA1, is present in the nuclei of all the EBV-infected cells. The process of EBNA1 tethering to the host cell chromosomes is critical to an efficient replication of the whole EBV genome. To our knowledge, there is no single agent that can both image and kill NPC tumor cells in the pharmaceutical market. The development of responsive EBNA1-targeting bio-probes can serve the purpose of having a dual function. Our invention can effectively target the dimerization interface of EBNA1 to disrupt its oncogenic function and kill the cancer cells, and can also emit a fluorescent signal when bound to the EBNA1 protein in these cells for imaging the EBV-associated cancers. This has shed some light to establish an anti-NPC agent with fewer side effects, and can also trace the presence of residual tumor cells after treatments.
The technology has dual-function: it can accurately trace and image for the EBV-associated cancers while being a pinpointed therapeutic intervention at the same time. Other than providing a fast, simple and accurate detection for EBV-associated cancers, our technology shows a high efficacy (less than 4mol/kg, ~92% cancer inhibition) toward cancer treatment.
Our invention shed important light to generate a new generation medical reagent and probe that has both imaging function and anti-tumour activity. The specificity of our technology provides a crucial means in accurate detection of EBV-associated cancer. More importantly, its anti-tumour ability provides the inhibition in the cancer cells and thus reduce time of delaying in therapy and potential metastasis.