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纳米结构功能共聚物生物缀合物整合素抑制剂。

Nanostructured functional co-polymers bioconjugate integrin inhibitors.

机构信息

Department of Chemistry, University of Rome Sapienza, P.le A. Moro 5, I-00185 Rome, Italy.

出版信息

J Colloid Interface Sci. 2011 Sep 15;361(2):465-71. doi: 10.1016/j.jcis.2011.05.041. Epub 2011 May 27.

Abstract

Synthesis and properties of bioconjugates based on functionalized polymeric nanoparticles (PNs) and monoclonal anti-Integrin αV CD51 (aI) antibody were investigated. Polymeric and co-polymeric colloidal nanoparticles with different functionalities, i.e., acid, amine, or thiol, namely poly(methylmethacrylate-co-acrylic acid) [P(MMA-co-AA)], poly(methylmethacrylate-co-dimethylpropargylamine) [P(MMA-co-DMPA)], poly(methylmethacrylate-co-allil mercaptane) [P(MMA-co-AM)], were obtained by tailoring emulsion synthesis and fully characterized by means of spectroscopic techniques and scanning electron microscopy (SEM). Bioconjugates (PN/aI) based on P(MMA) or P(MMA-co-AA) were obtained by loading the polymeric nanoparticles with the antibody anti-Integrin with a simple and straightforward immobilization strategy. Bioconjugates qualitative and quantitative loading analyses were carried out by means of polyacrylamide gel electrophoresis 1D-PAGE, MALDI-TOF, and LC/ESI-MS/MS investigations. The biological efficacy of bioconjugates was confirmed by the reduced migration potential of PN/aI-treated human kidney cells (HEK293). The easy immobilization procedure and high immobilization capacity of polymeric nanoparticles together with tuneable chemical functionalities and dimension of the polymeric nanoparticles open applicative perspectives for targeted delivery.

摘要

研究了基于功能化聚合物纳米粒子(PN)和单克隆抗整合素αV CD51(aI)抗体的生物缀合物的合成和性质。通过调整乳液合成获得了具有不同功能的聚合物和共聚物胶体纳米粒子,即聚(甲基丙烯酸甲酯-共-丙烯酸)[P(MMA-co-AA)]、聚(甲基丙烯酸甲酯-共-二甲基丙烯酰胺)[P(MMA-co-DMPA)]、聚(甲基丙烯酸甲酯-全硫醇)[P(MMA-co-AM)],并通过光谱技术和扫描电子显微镜(SEM)进行了充分表征。通过简单直接的固定化策略,将抗体抗整合素负载在聚合物纳米粒子上,得到了基于 P(MMA)或 P(MMA-co-AA)的生物缀合物(PN/aI)。通过 1D-PAGE、MALDI-TOF 和 LC/ESI-MS/MS 研究进行了生物缀合物的定性和定量负载分析。PN/aI 处理的人肾细胞(HEK293)迁移潜力降低证实了生物缀合物的生物学功效。聚合物纳米粒子的易于固定化程序和高固定化能力以及可调谐的化学功能和聚合物纳米粒子的尺寸为靶向递药开辟了应用前景。

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