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表面功能化树枝状聚合物作为肿瘤靶向的控释递药纳米系统。

Surface functionalized dendrimers as controlled-release delivery nanosystems for tumor targeting.

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.

出版信息

Eur J Pharm Sci. 2018 Sep 15;122:311-330. doi: 10.1016/j.ejps.2018.07.020. Epub 2018 Jul 9.

Abstract

Dendrimers are nano-sized and three-dimensional macromolecules with well-defined globular architecture and are widely used in various aspects such as drug and gene delivery owing to multivalent and host-guest entrapment properties. However, dendrimers like other nanomaterials have some disadvantages for example rapid clearance by reticuloendothelial system, toxicity due to interaction of amine terminated group with cell membrane, low transfection efficiency and lack of controlled release behavior, which reduce their therapeutic efficiency. To solve these problems, surface functionalization of dendrimers can be carried out. Surface functionalization not only mitigates this obstacle but also renders excessive specificity to dendrimer to improve efficiency of cancer therapy. Specific properties in cancer cell compared to normal cells such as overexpression of various receptors and difference in biological condition like pH, temperature and redox of tumor environment can be an appropriate strategy to increase site-specific targeting efficiency. Therefore, in this article we focus on numerous functionalization strategies, which are used in the modification of dendrimers through attachment of lipid, amino acid, protein/peptide, aptamer, vitamin, antibody. Moreover, increased biocompatibility, site-specific delivery based on various ligands, enhanced transfection efficiency, sustained and controlled release behavior based on stimuli responsiveness are benefits of functionalized dendrimer which we discuss in this review. Overall, these functionalized dendrimers can open a new horizon in the field of targeted drug and gene delivery.

摘要

树状聚合物是具有明确球形结构的纳米级三维大分子,由于具有多价和主体-客体包埋的特性,广泛应用于药物和基因传递等各个领域。然而,与其他纳米材料一样,树状聚合物也存在一些缺点,例如网状内皮系统的快速清除、由于末端胺基团与细胞膜相互作用而产生的毒性、低转染效率和缺乏控制释放行为,这些都会降低其治疗效果。为了解决这些问题,可以对树状聚合物进行表面功能化。表面功能化不仅可以减轻这一障碍,还可以使树状聚合物具有过度的特异性,从而提高癌症治疗的效率。与正常细胞相比,癌细胞具有许多特定的性质,如各种受体的过度表达,以及肿瘤环境的生物学条件(如 pH 值、温度和氧化还原状态)的差异,可以成为提高靶向效率的适当策略。因此,在本文中,我们重点介绍了许多功能化策略,这些策略通过连接脂质、氨基酸、蛋白质/肽、适体、维生素和抗体来修饰树状聚合物。此外,功能化树状聚合物具有增加的生物相容性、基于各种配体的特异性递药、增强的转染效率、基于刺激响应的持续和控制释放行为等优点,我们在这篇综述中进行了讨论。总的来说,这些功能化的树状聚合物可以为靶向药物和基因传递领域开辟新的前景。

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