Delivery of cancer therapeutics to extracellular and intracellular targets: Determinants, barriers, challenges and opportunities.
Delivery of cancer therapeutics to extracellular and intracellular targets: Determinants, barriers, challenges and opportunities.
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DOI：
10.1016/j.addr.2015.12.002
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发表时间：
2016-02-01
影响因子：
16.1
通讯作者：
Wientjes MG
中科院分区：
文献类型：
--
作者：
Au JL;Yeung BZ;Wientjes MG;Lu Z;Wientjes MG
分子医学的进步已经导致鉴定有价值的细胞和分子靶标位于细胞外和细胞内隔室。肿瘤治疗的有效性部分受到肿瘤间质递送和运输不足的限制。本报告的第一部分和第二部分概述了将治疗药物输送到预期靶点的动力学过程，肿瘤微环境和细胞外基质（TME/ECM）中的运输障碍，以及克服这些障碍的实验方法。第三部分讨论了纳米粒子-生物冕复合物的新概念和新发现，包括TME/ECM的作用。第四部分概述了癌症纳米疗法在动物到人类翻译中的挑战。第五部分概述了TME/ECM在免疫检查点抑制治疗中的背景、现状和作用，这是最新的癌症治疗方式。第六部分概述了多尺度计算模型的发展和使用，以捕捉不可避免的肿瘤异质性，多种非线性动力学过程，包括间质和跨血管运输以及癌症治疗药物与TME/ECM之间的相互作用，以便基于实验体外生物界面相互作用数据预测治疗药物的体内肿瘤空间动力学。第七部分提供了使用定量系统药理学方法的翻译研究的观点。
Advances in molecular medicine have led to identification of worthy cellular and molecular targets located in extracellular and intracellular compartments. Effectiveness of cancer therapeutics is limited in part by inadequate delivery and transport in tumor interstitium. Parts I and II of this report give an overview on the kinetic processes in delivering therapeutics to their intended targets, the transport barriers in tumor microenvironment and extracellular matrix (TME/ECM), and the experimental approaches to overcome such barriers. Part III discusses new concepts and findings concerning nanoparticle-biocorona complex, including the effects of TME/ECM. Part IV outlines the challenges in animal-to-human translation of cancer nanotherapeutics. Part V provides an overview of the background, current status, and the roles of TME/ECM in immune checkpoint inhibition therapy, the newest cancer treatment modality. Part VI outlines the development and use of multiscale computational modeling to capture the unavoidable tumor heterogeneities, the multiple nonlinear kinetic processes including interstitial and transvascular transport and interactions between cancer therapeutics and TME/ECM, in order to predict the in vivo tumor spatiokinetics of a therapeutic based on experimental in vitro biointerfacial interaction data. Part VII provides perspectives on translational research using quantitative systems pharmacology approaches.
DOI：
10.1111/j.1349-7006.1988.tb00050.x
发表时间：
1988-07
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Abe I;Hori K;Saito S;Tanda S;Li YL;Suzuki M
通讯作者：
Suzuki M