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Background In recent years, targeted drug delivery strategies have received special attention from the scientific world due to advantages such as more effective therapy and reduction of side effects. The principle of operation is delayed excretion from the bloodstream of the drug delivery system compared to the drug itself, as well as facilitated penetration into diseased cells thanks to the use of ligands recognized by appropriate receptors. Particularly interesting drug carriers are amphiphilic copolymers that form nano-sized micelles with a drug, which can release the drug at a specific place in the body under the influence of appropriate stimuli. Results We describe the synthesis of the diblock polymer, poly(2-hydroxyethyl acrylate)- b -poly( N -vinylcaprolactam) using RAFT/MADIX  (Reversible Addition-Fragmentation chain Transfer/MAcromolecular Design by Interchange of Xanthate ) controlled polymerization affording polymers with good dispersity according to SEC ( Size-Exclusion Chromatography ). Some post-modifications of the polymer with folic acid were then performed as evidenced by NMR ( Nuclear Magnetic Resonance ), UV–Vis ( UltraViolet–Visible ) and FT-IR ( Fourier-Transform Infrared)  spectroscopy, and TGA ( ThermoGravimetric Analysis ). The formation of stable micellar systems from polymers with and without the drug, 5-fluorouracil, was confirmed by DLS ( Dynamic Light Scattering ) and zeta potential measurements, and TEM ( Transmission Eelectron Microscopy ) imaging. Finally, the cloud point of the polymers was investigated, which turned out to be close to the temperature of the human body. Most importantly, these micellar systems have been explored as a drug delivery system against colon cancer, showing increased cytotoxicity compared to the drug alone. This effect was achieved due to the easier cellular uptake by the interaction of folic acid and its receptors on the surface of cancer cells. Conclusions The presented results constitute a solid foundation for the implementation of a nano-sized drug delivery system containing folic acid for practical use in the treatment of drug-resistant cancer, as well as more effective therapy with fewer side effects. Graphical Abstract

Synergistic effect of folate-conjugated polymers and 5-fluorouracil in the treatment of colon cancer