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.

中文翻译：

---

一种新型两亲性聚降冰片烯的合成、偶联能力和生物相容性评价

摘要 聚降冰片烯是通过“活性”和“受控”开环复分解聚合 (ROMP) 方法制备的，已成为一类对刺激敏感的新型聚合物载体。在此，我们报道了一种新型两亲双嵌段聚降冰片烯 PNCHO-b-PNTEG，它含有活性苯甲醛单元，通过 pH 敏感的席夫碱键与含氨基分子（例如阿霉素 (DOX)）表现出良好的共轭能力。通过 1H NMR、13C NMR、凝胶渗透色谱等多种技术对共聚物及其与 DOX 的偶联物 DOX-PNCHO-b-PNTEG 进行了充分分析。特别是，形成的 DOX-PNCHO-b-PNTEG 偶联物可以自-组装成直径为 81 ± 10 nm 的近球形胶束，并表现出酸触发的 DOX 释放行为，并且可以通过改变环境pH值来调节释放速率。PNCHO-b-PNTEG 出色的生物安全性通过对小鼠成纤维细胞（L-929 细胞）的体外毒性评估和斑马鱼胚胎急性发育毒性和细胞死亡的体内评估结果进一步证明。因此，本发明的基于聚降冰片烯的 PNCHO-b-PNTEG 作为生物相容性聚合物载体具有巨大的应用潜力，可用于制备各种 pH 敏感的偶联物。