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一种新型两亲性聚降冰片烯的合成、共轭能力及生物相容性评价

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

作者信息

He Hengxi, Song Bin, Qiu Guirong, Wang Weixiang, Gu Haibin

机构信息

Key Laboratory of Leather Chemistry and Engineering of Ministry of Education, Sichuan University, Chengdu, China.

College of Food and Bioengineering, Xihua University, Chengdu, China.

出版信息

Des Monomers Polym. 2020 Aug 30;23(1):141-154. doi: 10.1080/15685551.2020.1812832.

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, , 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, , were adequately analyzed by various techniques including H NMR, C NMR, gel permeation chromatography, etc. Especially, the formed conjugate of 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 was further demonstrated by the results from both toxicity evaluation to murine fibroblast cells (L-929 cells) and evaluation of acute developmental toxicity and cell death in zebrafish embryos. Hence, the present polynorbornene-based possesses great potential application as a biocompatible polymeric carrier and could be employed to fabricate various pH-sensitive conjugates.

摘要

通过“活性”和“可控”开环易位聚合(ROMP)方法制备的聚降冰片烯,已成为一类新型的刺激敏感型聚合物载体。在此,我们报道了一种新型两亲性二嵌段聚降冰片烯,含有活性苯甲醛单元,其通过pH敏感的席夫碱键对含氨基分子(如阿霉素(DOX))表现出良好的共轭能力。通过包括1H NMR、13C NMR、凝胶渗透色谱等各种技术对共聚物及其与DOX的共轭物进行了充分分析。特别是,所形成的共轭物能够自组装成直径为81±10nm的近球形胶束,并表现出酸触发的DOX释放行为,且释放速率可通过改变环境pH值进行调节。对小鼠成纤维细胞(L-929细胞)的毒性评估以及斑马鱼胚胎急性发育毒性和细胞死亡的评估结果进一步证明了其优异的生物安全性。因此,目前基于聚降冰片烯的共轭物作为生物相容性聚合物载体具有巨大的潜在应用价值,可用于制备各种pH敏感的共轭物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c698/7473315/6ec9b64b7b25/TDMP_A_1812832_UF0001_OC.jpg

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