Abstract
BACKGROUND: Theranostics, also known as personalized medicine, precision medicine, stratified medicine or P4 medicine, is a modern trend in treating diseases. The large part of that is the immunotheranostics, which applies monoclonal antibodies as molecular recognizing elements (MoRE) to interact specifically and block functioning of therapeutically important target. In terms of therapeutic application, being the proteins, antibodies has both advantages and disadvantages: the critical ones are specificity and immunogenisity, respectively. MoRE made of nucleic acids instead of polypeptides is coined as Aptamers. Aptamers are more robust to produce, handle and applied, not mentioning the lack to provoke an immune response. Therefore, some attempts are made to create aptamers to block glioma proliferation. Among them are the following aptamers: for EphB2/3 receptors, for PDGFRβ, to U87-EGFRvIII cells, GBI-10 to tenascin-C, AS1411 to nucleolin, DNA aptamers from whole-cell SELEX. Some applications of aptamers have been developed: surface-immobilized aptamers for cancer cell isolation and cytology, quantum dot-labeled aptamer nanoprobes, aptamer guided gadolinium-loaded liposomes, aptamer functionalization of nanosystems to get through the blood-brain barrier, microRNA-based targeted to eradicate glioblastoma stem-like cells, aptamer conjugated magnetic nanoparticles as nanosurgeons. In this research EGFR has been selected as specific target to explore interaction with aptamers in details for the further possibility to halt proliferation of EGFR positive clones of glioblastoma (GBM). MATERIAL AND METHODS: All published aptamer sequences, both DNA and RNA, have been collected and analyzed in terms of possible structures, gaining to find putative scaffold and recognizing parts of aptamers. All promising candidates were checked for affinity to the immobilized extracellular domain of human EGFR protein by surface plasmon resonance, as well as compare with commercial monoclonal antibodies. Derivatives of active aptamers were made to reveal putative scaffold and recognizing domain, and again check the affinity. Studying of interactions of several aptamers with EGFR positive cell lines and clones of surgical samples of GBM were made. RESULTS: A particular aptamer, NA511, has a very promising properties, both structural and functional. It shows distinctive putative structure which is easy to modify; it exhibits affinity similar to commercial antibodies. Therefore, it could be a promising candidate to translate this MoRE for theranostics of GMB. CONCLUSION: In spite of many aptamers for EGFR had been published till now, most of them do not have an obvious potential for further development. Therefore, a methodology has to be developed yet for translation of the aptamers into the theranostic drugs. The work was supported by Grant RFBR KOMFI 17-00-00162 (K), 17-00-00160.