The effectiveness of chemotherapy is still required to be improved by combating new pharmacological targets and overcoming multidrug resistance (MDR). New nano-scale drug delivery systems can increase the efficiency of anticancer drugs and fight against MDR. Macrocyclic molecules such as dynarene and calixarene derivatives have potent anticancer effects by interacting with cancer-related biomolecules. At the same time, they act as nanocontainers for the delivery of drugs, similar to cyclodextrins (CD).

Our previous results showed, that by the combined application of these macrocycles, supramolecular structures can be formed, enhancing the solubilization of the drug and applying the pharmacological effects of the macrocycles. In NextNano4Cancer project macrocycles together with CD will be used for the formation of larger supramolecular complexes for the solubilization and delivery of new casein kinase 2 inhibitors (CK2i). The project aims to reach the TRL 5 of a new chemotherapeutic injectable formulation containing the above-mentioned components in a self-associated nanosystem. In the frame of the project, macrocyclic molecules and CK2i will be synthetized and tested for their interactions by molecular modelling and solubilization studies.

The best compositions will be applied to form a ternary supramolecular system containing CK2i+calixarene/dynarene+CD. The pharmacological efficiency of the product will be tested on cancer cell lines and on animal cancer models. Special attention will be paid for the feasibility study of the scale-up in the field of synthesis and formulation. At the end of the project a scale-up plan for manufacturing will be constructed and a GMP process development will be initiated. The effectiveness of the macrocycle-based supramolecular systems combined with anticancer agents has not been tested yet and their combined formulation has not been presented, thus this system will attract significant scientific and societal interest.