Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery.
Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery.
复制标题
调节肿瘤微环境以增强肿瘤纳米药物的输送
DOI：
10.3389/fphar.2017.00952
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发表时间：
2017
影响因子：
5.6
通讯作者：
Pang Z
中科院分区：
文献类型：
--
作者：
Zhang B;Hu Y;Pang Z
基于增强渗透性和滞留(EPR)效应的纳米药物，包括脂质体、胶束和纳米粒，由于其优于传统抗癌药物，已成为肿瘤治疗的主流。先进的纳米药物设计，包括主动靶向纳米药物、肿瘤响应性纳米药物以及优化物理化学性质，使纳米药物能够高效地输送到肿瘤，进一步提高了它们的治疗效果。然而，这些策略仍然不能克服肿瘤微环境中血流不均、细胞外基质致密、基质细胞丰富和间质流体压力高等传递障碍，严重损害了纳米药物的血管运输，阻碍了它们的有效外渗，阻碍了它们的间质运输，实现了肿瘤内的均匀分布。因此，调节肿瘤微环境已成为改善纳米药物向肿瘤靶向传递的重要策略。本文综述了现有的调节肿瘤微环境的策略和方法，以改善肿瘤的血流灌注，帮助更多的纳米药物到达肿瘤部位，促进纳米药物的外渗，促进血管的转运，并改善间质转运，以优化纳米药物的分布。这些策略可能为开发新的联合化疗方案和重新评估以前不太理想的药物提供了一条途径。
Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.
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影响因子：
10.3
作者：
Brennen, W. Nathaniel;Rosen, D. Marc;Denmeade, Samuel R.
通讯作者：
Denmeade, Samuel R.
DOI：
10.1073/pnas.1312197110
发表时间：
2013-10-01
影响因子：
11.1
作者：
Cieslewicz, Maryelise;Tang, Jingjing;Pun, Suzie H.
通讯作者：
Pun, Suzie H.
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
DOI：
10.1073/pnas.86.14.5385
发表时间：
1989-07-01
影响因子：
11.1
作者：
CHARY, SR;JAIN, RK
通讯作者：
JAIN, RK