Bioactive moieties designed to bind to cell membrane receptors benefit from coupling with polymeric carriers that have enhanced affinity to the cell membrane. When bound to the cell surface, such carriers create a "2D solution" of a ligand with a significantly increased concentration near a membrane-bound receptor compared to a freely water-soluble ligand. Bifunctional polymeric carriers based on amphiphilic triblock copolymers were synthesized from 2-pent-4-ynyl oxazoline, 2-nonyl oxazoline and 2-ethyl oxazoline. Their self-assembly and interactions with plasma proteins and HEK 293 cells were studied in detail. The affinity of these triblock copolymers to HEK 293 cell membranes and organ tissues was tunable by the overall hydrophobicity of the polymer molecule, which is determined by the length of the hydrophobic and hydrophilic blocks. The circulation time and biodistribution of three representative triblock copolymers were monitored after intravenous administration to C57BL/6 albino mice. A prolonged circulation time was observed for polymers with longer hydrophobic blocks, despite their molecular weight being below the renal threshold.

Center for Advanced Preclinical Imaging 1st Faculty of Medicine Charles University Salmovská 3 Prague 2 Czechia

Environmental Electron Microscopy Group Institute of Scientific Instruments of the Czech Academy of Sciences Královopolská 147 61 200 Brno Czechia

Institute of Macromolecular Chemistry of the Czech Academy of Sciences Heyrovského n 1888 2 162 06 Prague 6 Czechia

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo n 542 2 160 00 Prague 6 Czechia

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo n 542 2 160 00 Prague 6 Czechia; Department of Genetics and Microbiology Faculty of Science Charles University Viničná 5 128 44 Prague 2 Czechia

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo n 542 2 160 00 Prague 6 Czechia; Laboratory of Theranostics Institute of Biochemistry and Experimental Oncology 1st Faculty of Medicine U Nemocnice 5 128 53 Prague 2 Czechia

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