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新型生物医学聚合物聚(2-异丙烯基-2-恶唑啉)细胞毒性和免疫调节特性的体外和体内研究

Ex Vivo and In Vitro Studies on the Cytotoxicity and Immunomodulative Properties of Poly(2-isopropenyl-2-oxazoline) as a New Type of Biomedical Polymer.

作者信息

Kroneková Zuzana, Mikulec Marcel, Petrenčíková Nadežda, Paulovičová Ema, Paulovičová Lucia, Jančinová Viera, Nosál' Radomír, Reddy Palem S, Shimoga Ganesh D, Chorvát Dušan, Kronek Juraj

机构信息

Department for Biomaterials Research, Polymer Institute, Slovak Academy of Sciences, Dubravska cesta 9, 845 41, Bratislava, Slovakia.

Institute of Chemistry, Center of Glycomics, Slovak Academy of Sciences, Dubravska cesta 9, 84236, Bratislava, Slovakia.

出版信息

Macromol Biosci. 2016 Aug;16(8):1200-11. doi: 10.1002/mabi.201600016. Epub 2016 May 6.

DOI:10.1002/mabi.201600016
PMID:27150385
Abstract

Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes. The cytotoxicities of 2-oxazoline monomers, PIPOx, and fluorescently labeled PIPOx are evaluated in vitro using an 3-(4,5-Dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and ex vivo using a cell proliferation assay with adenosine triphosphate bioluminescence. The cell uptake of labeled PIPOx is used to determine the colocalization of PIPOx with cell organelles that are part of the endocytic pathway. For the first time, it is shown that poly(2-isopropenyl-2-oxazoline) is a biocompatible material and is suitable for biomedical applications; further, its immunomodulative properties are evaluated.

摘要

聚(2-链烯基-2-恶唑啉)是一类很有前景的功能聚合物,可用于多种生物医学应用,如药物递送系统、肽缀合物或基因递送。在本研究中,聚(2-异丙烯基-2-恶唑啉)(PIPOx)通过偶氮二异丁腈引发的自由基聚合反应制备。侧链中的活性恶唑啉单元支持与不同的含羧基化合物发生加成反应,这有助于制备用两种不同荧光染料标记的聚合物。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑法在体外评估2-恶唑啉单体、PIPOx和荧光标记的PIPOx的细胞毒性,并使用三磷酸腺苷生物发光细胞增殖试验在体内评估其细胞毒性。利用标记的PIPOx的细胞摄取来确定PIPOx与作为内吞途径一部分的细胞器的共定位。首次表明聚(2-异丙烯基-2-恶唑啉)是一种生物相容性材料,适用于生物医学应用;此外,还评估了其免疫调节特性。

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