Juillerat-Jeanneret L, Schmitt F
University Institute of Pathology, Bugnon 25, CH-1011 Lausanne, Switzerland.
Med Res Rev. 2007 Jul;27(4):574-90. doi: 10.1002/med.20086.
Most therapeutic drugs distribute to the whole body, which results in general toxicity and poor acceptance of the treatments by patients. The targeted delivery of chemotherapeutics to defined cells, either stromal or cancer cells in cancer lesions, or defined inflammatory cells in immunological disorders, is one of the main challenges and a very active field of research in the development of treatment strategies to minimize side-effects of drugs. Disease-associated cells express molecules, including proteases, receptors, or adhesion molecules, that are different or differently expressed than their normal counterparts. Therefore one goal in the field of targeted therapies is to develop chemically derivatized drugs or drug vectors able to target defined cells via specific recognition mechanisms and also able to overcome biological barriers. This article will review the approaches which have been explored to achieve these goals and will discuss in more detail three examples (i) the use of nanostructures to take advantage of increased vascular permeability in some human diseases, (ii) the targeting of therapeutic drugs to an organ, the brain, protected against foreign molecules by the blood-brain barrier, and (iii) the use of the folate receptor to target either tumor cells or activated macrophages.
大多数治疗药物会分布到全身，这会导致全身毒性以及患者对治疗的接受度较低。将化疗药物靶向递送至特定细胞，无论是癌症病灶中的基质细胞或癌细胞，还是免疫紊乱中的特定炎症细胞，都是主要挑战之一，也是开发治疗策略以尽量减少药物副作用这一研究领域中非常活跃的一个方向。疾病相关细胞表达的分子，包括蛋白酶、受体或黏附分子，与正常对应细胞不同或表达情况不同。因此，靶向治疗领域的一个目标是开发能够通过特定识别机制靶向特定细胞且还能克服生物屏障的化学衍生药物或药物载体。本文将综述为实现这些目标而探索的方法，并更详细地讨论三个例子：（i）利用纳米结构来利用某些人类疾病中增加的血管通透性；（ii）将治疗药物靶向血脑屏障保护其免受外来分子影响的器官——大脑；（iii）利用叶酸受体靶向肿瘤细胞或活化巨噬细胞。
