DDS Research Institute, Sojo University, Ikeda, Kumamoto, Japan.
Adv Drug Deliv Rev. 2013 Jan;65(1):71-9. doi: 10.1016/j.addr.2012.10.002. Epub 2012 Oct 23.
The EPR effect results from the extravasation of macromolecules or nanoparticles through tumor blood vessels. We here provide a historical review of the EPR effect, including its features, vascular mediators found in both cancer and inflamed tissue. In addition, architectural and physiological differences of tumor blood vessels vs that of normal tissue are commented. Furthermore, methods of augmentation of the EPR effect are described, that result in better tumor delivery and improved therapeutic effect, where nitroglycerin, angiotensin I-converting enzyme (ACE) inhibitor, or angiotensin II-induced hypertension are employed. Consequently, better therapeutic effect and reduced systemic toxicity are generally observed. Obviously, the EPR effect based delivery of nanoprobes are also useful for tumor-selective imaging agents with using fluorescent or radio nuclei in nanoprobes. We also commented a key difference between passive tumor targeting and the EPR effect in tumors, particularly as related to drug retention in tumors: passive targeting of low-molecular-weight X-ray contrast agents involves a retention period of less than a few minutes, whereas the EPR effect of nanoparticles involves a prolonged retention time-days to weeks.
EPR 效应是由于大分子或纳米颗粒通过肿瘤血管外渗引起的。我们在这里回顾了 EPR 效应，包括其特征，以及在癌症和炎症组织中发现的血管介质。此外，还评论了肿瘤血管与正常组织在结构和生理上的差异。此外，还描述了增强 EPR 效应的方法，这些方法可导致更好的肿瘤传递和改善治疗效果，其中使用了硝化甘油、血管紧张素转换酶 (ACE) 抑制剂或血管紧张素 II 诱导的高血压。因此，通常会观察到更好的治疗效果和降低的全身毒性。显然，基于 EPR 效应的纳米探针递药也可用于肿瘤选择性成像剂，在纳米探针中使用荧光或放射性核素。我们还评论了被动肿瘤靶向与肿瘤中 EPR 效应之间的一个关键区别，特别是与肿瘤中药物滞留有关：低分子量 X 射线造影剂的被动靶向涉及不到几分钟的滞留时间，而纳米颗粒的 EPR 效应涉及延长的滞留时间——几天到几周。
