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药物研究中的树枝状大分子。

Dendrimers in drug research.

作者信息

Boas Ulrik, Heegaard Peter M H

机构信息

Department of Immunology and Biochemistry, Danish Veterinary Institute, Bülowsvej 27, Copenhagen, DK-1790, Denmark.

出版信息

Chem Soc Rev. 2004 Jan 10;33(1):43-63. doi: 10.1039/b309043b. Epub 2003 Dec 5.

Abstract

Dendrimers are versatile, derivatisable, well-defined, compartmentalised chemical polymers with sizes and physicochemical properties resembling those of biomolecules e.g. proteins. The present critical review (citing 158 references) briefly describes dendrimer design, nomenclature and divergent/convergent dendrimer synthesis. The characteristic physicochemical features of dendrimers are highlighted, showing the effect of solvent pH and polarity on their spatial structure. The use of dendrimers in biological systems are reviewed, with emphasis on the biocompatibility of dendrimers, such as in vitro and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples are the use of dendrimers as 'glycocarriers' for the controlled multimeric presentation of biologically relevant carbohydrate moieties which are useful for targeting modified tissue in malignant diseases for diagnostic and therapeutic purposes. Finally, the use of specific types of dendrimers as scaffolds for presenting vaccine antigens, especially peptides, for use in vaccines is presented.

摘要

树枝状聚合物是多功能的、可衍生化的、结构明确的、具有分隔结构的化学聚合物,其大小和物理化学性质类似于生物分子,如蛋白质。本综述(引用158篇参考文献)简要描述了树枝状聚合物的设计、命名以及发散/收敛型树枝状聚合物的合成。重点介绍了树枝状聚合物的特征物理化学特性,展示了溶剂pH值和极性对其空间结构的影响。综述了树枝状聚合物在生物系统中的应用,重点关注树枝状聚合物的生物相容性,如体外和体内细胞毒性,以及生物渗透性、生物稳定性和免疫原性。该综述探讨了树枝状聚合物作为生物特异性识别、抑制和靶向中生物配体高效多价呈现工具的众多应用。树枝状聚合物可用作抗菌和抗病毒治疗的药物,并已被用作抗肿瘤剂。综述强调了树枝状聚合物作为药物或基因递送载体在例如抗癌治疗中的应用,并描述了针对医学应用的不同主客体结合基序的设计。其他具体例子包括将树枝状聚合物用作“糖载体”,用于生物相关碳水化合物部分的可控多聚体呈现,这对于恶性疾病中靶向修饰组织以进行诊断和治疗目的很有用。最后,介绍了使用特定类型的树枝状聚合物作为呈现疫苗抗原(特别是肽)的支架用于疫苗的情况。

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