Synthesis and characterization of amphiphilic poly(pseudo-amino acid) polymers containing a nucleobase

In this study, we developed novel bioresorbable amphiphilic poly(pseudo-amino acid)s containing nucleobases. These polymers were synthesized by the condensation polymerization of N-benzyloxycarbonyl-4-hydroxyl-L-proline (NZHpr), followed by the coupling of an alkynyl-functionalized nucleobase derivative to the azido-end group of PNZHpr_n. These polymers were characterized by ultraviolet-visible, fluorescence, nuclear magnetic resonance, infrared spectroscopy and gel permeation chromatography. The nucleobase-terminated PNZHpr_n polymers formed micelles in an aqueous phase. The critical micelle concentrations ranged from 1.51 to 16.90 mgl^-1. Vesicular or spherical micellar structures were observed, depending on the nucleobase coupled. Nucleobase-PNZHpr_n selectively bound to complementary small molecules. The micelles were observed to release drugs rapidly in an acidic environment. An in vitro cell viability assay indicated that nucleobase-terminated PNZHprn exhibited low cytotoxicity. doxorubicin (DOX)-loaded micelles facilitated drug release more effectively compared with free DOX based on the uptake by human cervical cancer (HeLa) cells. Furthermore, these micelles were primarily retained in the cytoplasm, whereas free DOX tended to accumulate in the nuclei.