Barrett Tristan, Ravizzini Gregory, Choyke Peter L, Kobayashi Hisataka
Molecular Imaging Program, NCI/NIH, Building 10, Room 1B40, MSC 1088, Bethesda, MD 20892-1088, USA.
IEEE Eng Med Biol Mag. 2009 Jan-Feb;28(1):12-22. doi: 10.1109/MEMB.2008.931012.
Dendrimers are a class of synthetically produced highly branched, spherical nanostructures that can be used as carrier molecules for imaging agents. A variety of dendrimers exist and each has biological properties that will alter its biodistribution. Dendrimers are composed of combinations of core types such as ethylene diamine (EDA), diaminobutyl (DAB), polyamidoamine (PAMAM) and polypropylimine (PPI) and different surface residues such as amine, carboxyl, and alcoholic groups. Increasing the number of primary amine groups attached to the core will increase the size of the dendrimer, which is known by the term ‘generation’ of the dendrimer. Because dendrimers are highly structured in size and shape and have a low poly-dispersity index, each dendrimer generation has distinct pharmacokinetic and pharmacodynamic properties which may prove advantageous for particular medical applications. Research has centered on developing these macromolecules as imaging agents for numerous modalities including magnetic resonance imaging, X-ray computed tomography, optical imaging and nuclear medicine. Another prospective function of dendrimers is as drug delivery vectors, whereby therapeutic payloads are encapsulated within the shell, or incorporated onto their multivalent surface, and targeted to tumor cells using ligands that specifically bind to cancer cells or in normal cells altered by nearby cancer cells. Furthermore, the larger size of high generation dendrimers offers potential to develop dual purpose agents that can act both as imaging agents and as delivery vectors, or can be imaged with more than one modality. Herein, we discuss the current and future applications of dendrimers in medicine and the central role they play in the emerging field of nanotechnology.
树枝状大分子是一类通过合成产生的高度分支的球形纳米结构,可作为成像剂的载体分子。存在多种树枝状大分子,每种都具有会改变其生物分布的生物学特性。树枝状大分子由诸如乙二胺(EDA)、二氨基丁基(DAB)、聚酰胺胺(PAMAM)和聚丙基亚胺(PPI)等核心类型与不同的表面残基(如胺基、羧基和醇基)组合而成。增加连接到核心的伯胺基团数量会增加树枝状大分子的尺寸,这由树枝状大分子的“代数”来表示。由于树枝状大分子在尺寸和形状上具有高度规整性且多分散指数较低,每种树枝状大分子代数都具有独特的药代动力学和药效学特性,这可能对特定医学应用具有优势。研究主要集中在将这些大分子开发为多种成像方式的成像剂,包括磁共振成像、X射线计算机断层扫描、光学成像和核医学。树枝状大分子的另一个潜在功能是作为药物递送载体,治疗性药物负载被封装在外壳内,或结合到其多价表面上,并使用与癌细胞或附近癌细胞改变的正常细胞特异性结合的配体靶向肿瘤细胞。此外,高代数树枝状大分子的较大尺寸为开发既能作为成像剂又能作为递送载体,或能用多种成像方式成像的两用剂提供了潜力。在此,我们讨论树枝状大分子在医学中的当前和未来应用以及它们在新兴的纳米技术领域中所起的核心作用。