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

• Published in: Polymer journal Vol. 46; no. 10; pp. 710 - 721
• Main Authors: Lee, Ren-Shen, Peng, Kang-Yu, Wang, Shiu-Wei, Li, You-Zhen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2014; Nature Publishing Group
• Subjects: 639/638/455/941; 639/638/455/953; 639/638/455/958; Biomaterials; Bioorganic Chemistry; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Derivatives; Drug delivery systems; Drugs; Fluorescence; Micelles; Nuclei; original-article; Polymer Sciences; Polymers; Surfaces and Interfaces; Surgical implants; Thin Films
• ISSN: 0032-3896; 1349-0540
• DOI: 10.1038/pj.2014.52

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 mg l −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 PNZHpr n 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. Amphiphilic poly(pseudo-amino acid) containing a nucleobase that was synthesized by coupling an alkynyl-functional nucleobase derivative to the azido-end group PNZHpr n . DOX-loaded micelles facilitated drug release more effectively in the uptake of DOX than in that of free DOX by HeLa cells.