Tomalia D A, Reyna L A, Svenson S
Dendritic Nanotechnologies Inc., 2625 Denison Drive, Mt. Pleasant, MI 48858, USA.
Biochem Soc Trans. 2007 Feb;35(Pt 1):61-7. doi: 10.1042/BST0350061.
Dendrimers are routinely synthesized as tuneable nanostructures that may be designed and regulated as a function of their size, shape, surface chemistry and interior void space. They are obtained with structural control approaching that of traditional biomacromolecules such as DNA/RNA or proteins and are distinguished by their precise nanoscale scaffolding and nanocontainer properties. As such, these important properties are expected to play an important role in the emerging field of nanomedicine. This review will describe progress on the use of these features for both targeted diagnostic imaging and drug-delivery applications. Recent efforts have focused on the synthesis and pre-clinical evaluation of a multipurpose STARBURST PAMAM (polyamidoamine) dendrimer prototype that exhibits properties suitable for use as: (i) targeted, diagnostic MRI (magnetic resonance imaging)/NIR (near-IR) contrast agents, (ii) and/or for controlled delivery of cancer therapies. Special emphasis will be placed on the lead candidate, namely [core: 1,4-diaminobutane; G (generation)=4.5], [dendri-PAMAM(CO(2)Na)(64)]. This dendritic nanostructure (i.e. approximately 5.0 nm diameter) was selected on the basis of a very favourable biocompatibility profile [The Nanotechnology Characterization Laboratory (NCL), an affiliate of the National Cancer Institute (NCI), has completed extensive in vitro studies on the lead compound and have found it to be very benign, non-immunogenic and highly biocompatible], the expectation that it will exhibit desirable mammalian kidney excretion properties and demonstrated targeting features.
树枝状大分子通常被合成成可调节的纳米结构,其可以根据尺寸、形状、表面化学性质和内部空隙空间进行设计和调控。它们的结构控制程度接近传统生物大分子(如DNA/RNA或蛋白质),并以其精确的纳米级支架和纳米容器特性而著称。因此,这些重要特性有望在新兴的纳米医学领域发挥重要作用。本综述将描述利用这些特性在靶向诊断成像和药物递送应用方面取得的进展。最近的努力集中在一种多功能星爆型聚酰胺-胺(PAMAM)树枝状大分子原型的合成和临床前评估上,该原型具有适合用作:(i)靶向诊断磁共振成像(MRI)/近红外(NIR)造影剂,(ii)和/或用于癌症治疗的可控递送的特性。将特别强调主要候选物,即[核心:1,4-二氨基丁烷;G(代数)=4.5],[树枝状-PAMAM(CO₂Na)₆₄]。这种树枝状纳米结构(即直径约5.0 nm)是根据非常良好的生物相容性概况选择的[纳米技术表征实验室(NCL)是美国国家癌症研究所(NCI)的附属机构,已对该先导化合物完成了广泛的体外研究,发现它非常良性、无免疫原性且具有高度生物相容性],预期它将表现出理想的哺乳动物肾脏排泄特性并具有已证实的靶向特征。