Synthesis, conjugating capacity and biocompatibility evaluation of a novel amphiphilic polynorbornene

Abstract

Polynorbornenes, prepared by the ‘living’ and ‘controlled’ ring-opening metathesis polymerization (ROMP) method, have emerged as a stimuli-sensitive new class of polymer carriers. Herein, we reported a novel amphiphilic diblock polynorbornene, PNCHO-b-PNTEG, containing active benzaldehyde units, which exhibited good conjugating capacity to amino-containing molecules (e.g., doxorubicin (DOX)) via the pH-sensitive Schiff base linkage. The copolymer and its conjugate with DOX, DOX-PNCHO-b-PNTEG, were adequately analyzed by various techniques including 1H NMR, 13C NMR, gel permeation chromatography, etc. Especially, the formed conjugate of DOX-PNCHO-b-PNTEG could self-assemble into near-spherical micelles with the diameter of 81 ± 10 nm, and exhibit acid-triggered DOX release behavior, and the release rate could be adjusted by changing the environmental pH value. The excellent biological safety of PNCHO-b-PNTEG was further demonstrated by the results from both in vitro toxicity evaluation to murine fibroblast cells (L-929 cells) and in vivo evaluation of acute developmental toxicity and cell death in zebrafish embryos. Hence, the present polynorbornene-based PNCHO-b-PNTEG possesses great potential application as a biocompatible polymeric carrier and could be employed to fabricate various pH-sensitive conjugates.

Keywords

• polynorbornene
• ring-opening metathesis polymerization
• polymeric carrier
• conjugate
• ph-responsive