Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging
Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging
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DOI：
10.1042/bst0350061
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发表时间：
2007-02-01
影响因子：
3.9
通讯作者：
Svenson, S.
中科院分区：
文献类型：
--
作者：
Tomalia, D. A.;Reyna, L. A.;Svenson, S.
树枝状聚合物通常被合成为可调节的纳米结构，其可以根据其尺寸、形状、表面化学和内部空隙空间来设计和调节。它们是通过接近传统生物大分子如DNA/RNA或蛋白质的结构控制获得的，并以其精确的纳米级支架和纳米容器特性而闻名。因此，这些重要的特性预计将在新兴的纳米医学领域发挥重要作用。这篇综述将描述这些功能在靶向诊断成像和药物输送应用中的应用进展。最近的努力集中在多用途PAMAM（聚酰胺胺）树状聚合物原型的合成和临床前评价上，该树状聚合物原型表现出适合用作以下的性质：（i）靶向的诊断MRI（磁共振成像）/NIR（近红外）造影剂，（ii）和/或用于癌症治疗的受控递送。将特别强调主要候选物，即[核心：1，4-二氨基丁烷; G（生成）= 4.5]，[树枝状-PAMAM（CO2 Na）（64）]。这种树枝状纳米结构基于非常有利的生物相容性特征选择了纳米技术表征实验室（NCL）（国家癌症研究所（NCI）的附属机构），已完成了对先导化合物的广泛体外研究，并发现其非常良性，非免疫原性和高度生物相容性），预期其将表现出期望的哺乳动物肾脏排泄特性并显示出靶向特征。
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 (R) 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(CO2Na)(64)]. This dendritic nanostructure (i.e. similar to 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.