The aim of the project is to obtain amphiphilic copolymers with a topology cyclic “brush”, consisting of a polymer cycle with multiple grafted side polymer chains. The amphiphilic nature of these cyclic polymer “brushes” will facilitate the formation of nanoscale particles (self- assembled structures, unimolecular micelles) in an aqueous media, that will be used for the transport and delivery of biologically active substances and oligo- and polynucleotides. By varying the nature and molar masses of the polymer cycle and grafted chains, as well as the grafting density, a wide variety of unique amphiphilic copolymers will be generated. These copolymers will serve as platforms for (1) transport and delivery of biologically active substances (drugs, pharmaceuticals), (2) transport and delivery of nucleic acids (DNA, RNA, plasmid), and (3) synthesis of spherical nucleic acids for the transport and delivery of oligonucleotides.
A variety of synthetic, preparation, and loading techniques (from methods for controlled polymerization to “click” or other highly effective reactions and specific approaches for preparation of self-assembled/co-assembled structures and unimolecular micelles) will be employed to design and synthesize cyclic polymer “brushes” and spherical nucleic acids and construct platforms for drug and nucleic acid delivery. After full physicochemical characterization in terms of size, size distribution, molar mass, dimensions of the cores, thickness of the shell, surface potential, etc., detailed investigation of the biological properties will follow. In particular, investigation of the cytotoxicity, biocompatibility, the active substance efficiency, the potential for controlled co-delivery of drugs, cellular internalization, and the ability to achieve transfection and gene silencing will be performed.
The implementation of the research program will bring to accumulation of knowledge as well as experimental data and findings, which are applicable for solving health problems with significant social importance such as treatment of cancer and genetic diseases, vaccine development, regenerative medicine, development of diagnostic and theragnostic platforms. Whereas the research planned in the project is entirely fundamental, an essential part of it has an innovation character and potential. The implementation of the project will contribute to improvement of the skills and qualification of the team members and enhancement of competitiveness of the partnering organizations.