Tumour-targeted drug and gene delivery: principles and concepts
Tumour-targeted drug and gene delivery: principles and concepts
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DOI：
10.1017/s1462399404008269
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发表时间：
2004-09-23
影响因子：
6.2
通讯作者：
Schaetzlein, Andreas G.
中科院分区：
文献类型：
--
作者：
Cassidy, Jim;Schaetzlein, Andreas G.
肿瘤靶向药物和基因递送：原理和概念肿瘤靶向的递送系统分为两个基本类别：药物缀合物系统，其中单个药物分子被化学修饰以使其直接靶向肿瘤;和基于载体的系统，其中药物或基因首先被非共价包装到合成载体中，然后靶向肿瘤。在这两种情况下，目标是最大限度地使靶细胞暴露于药物，同时最大限度地减少由正常组织中的非特异性毒性引起的副作用。这种剂量差异的产生是基于肿瘤和身体其他部位之间的表型差异。然而，尽管广泛的这种变化与正常细胞向癌细胞的转化有关，但不存在单一的共同特征来允许明确靶向肿瘤。此外，肿瘤微环境会产生物理屏障，显著损害肿瘤内的转运。因此，重要的是使药物的递送要求与递送系统的能力相匹配。在这篇综述中，简要概述了有助于指导这种肿瘤靶向策略发展的基本概念和原则。
Tumour-targeted drug and gene delivery: principles and concepts Delivery systems for tumour targeting fall into two basic categories: drug conjugate systems, in which individual drug molecules are chemically modified to target them directly to the tumour; and carrier-based systems, in which the drug or gene is first packaged non-covalently into a synthetic carrier that is then targeted to the tumour. In both cases, the objective is to maximise exposure of the target cells to the drug yet minimise side effects that result from nonspecific toxicity in normal tissues. The creation of such dose differentials is based on phenotypic differences between the tumour and the rest of the body. However, although a wide range of such changes have been linked to the transformation of normal cells to cancer cells, no single common feature exists to allow unambiguous targeting to the tumour. In addition, the tumour microenvironment creates physical barriers that significantly impair transport within the tumour. It is therefore important to match the delivery requirements of the drug to the capabilities of the delivery system. In this review, a brief overview is given of the underlying concepts and principles that help guide the development of such tumour-targeting strategies.