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Pharmacological and physical vessel modulation strategies to improve EPR-mediated drug targeting to tumors
Advanced Drug Delivery Reviews ( IF 15.2 ) Pub Date : 2017-07-08 , DOI: 10.1016/j.addr.2017.07.007
Tarun Ojha 1 , Vertika Pathak 2 , Yang Shi 2 , Wim E Hennink 3 , Chrit T W Moonen 4 , Gert Storm 5 , Fabian Kiessling 2 , Twan Lammers 6
Affiliation  

The performance of nanomedicine formulations depends on the Enhanced Permeability and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems, such as liposomes, polymers and micelles, aim to exploit the EPR effect to accumulate at pathological sites, to thereby improve the balance between drug efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not yet managed to achieve convincing therapeutic results, at least not in large cohorts of patients. This is likely mostly due to high inter- and intra-patient heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and predict EPR, another strategy to address this heterogeneity is the establishment of vessel modulation strategies to homogenize and improve EPR. Over the years, several pharmacological and physical co-treatments have been evaluated to improve EPR-mediated tumor targeting. These include pharmacological strategies, such as vessel permeabilization, normalization, disruption and promotion, as well as physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and phototherapy. In the present manuscript, we summarize exemplary studies showing that pharmacological and physical vessel modulation strategies can be used to improve tumor-targeted drug delivery, and we discuss how these advanced combination regimens can be optimally employed to enhance the (pre-) clinical performance of tumor-targeted nanomedicines.



中文翻译:


改善 EPR 介导的肿瘤药物靶向的药理学和物理血管调节策略



纳米药物制剂的性能取决于增强渗透性和保留(EPR)效应。基于原型纳米药物的药物递送系统,例如脂质体、聚合物和胶束,旨在利用EPR效应在病理部位积累,从而改善药物疗效和毒性之间的平衡。然而,迄今为止,针对肿瘤的纳米药物尚未取得令人信服的治疗结果,至少在大量患者中是这样。这可能主要是由于 EPR 中患者间和患者内部的高度异质性。除了开发(成像)生物标志物来监测和预测 EPR 之外,解决这种异质性的另一个策略是建立血管调节策略来均质化和改善 EPR。多年来,人们对几种药物和物理联合治疗进行了评估,以改善 EPR 介导的肿瘤靶向。这些包括药理学策略,例如血管通透性、正常化、破坏和促进,以及通过热疗、放射治疗、声孔治疗和光疗增强物理 EPR。在本手稿中,我们总结了示范性研究,表明药理学和物理血管调节策略可用于改善肿瘤靶向药物输送,并讨论如何最佳地采用这些先进的组合方案来增强肿瘤的(前)临床表现。肿瘤靶向纳米药物。

更新日期:2017-07-08
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