Multi-modal strategies for overcoming tumor drug resistance: hypoxia, the Warburg effect, stem cells, and multifunctional nanotechnology.
Multi-modal strategies for overcoming tumor drug resistance: hypoxia, the Warburg effect, stem cells, and multifunctional nanotechnology.
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DOI：
10.1016/j.jconrel.2011.03.032
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发表时间：
2011-10-30
期刊：
影响因子：
--
通讯作者：
Amiji M
中科院分区：
文献类型：
--
作者：
Milane L;Ganesh S;Shah S;Duan ZF;Amiji M
肿瘤多药耐药（MDR）的发生与肿瘤细胞的生存和微环境选择压力有关。MDR的特征包括异常血管、缺氧区域、ABC转运蛋白上调、有氧糖酵解和升高的凋亡阈值。纳米尺寸的递送载体是治疗MDR癌症的理想载体，因为它们可以提高药物的治疗指数，并且它们可以被工程化以实现多功能参数。纳米载体的多功能性使其比传统化疗更适合治疗异质性肿瘤。纳米载体还通过EPR效应具有优先的肿瘤积累;这种积累可以通过主动靶向MDR细胞的生物学特征来进一步增强。也许使用纳米载体药物递送治疗MDR癌症的最显著益处是纳米载体递送转移ABC转运蛋白介导的药物外排的作用;这是MDR的主要机制。本文综述了多功能纳米载体治疗MDR的能力、应用和实例。本文重点介绍了提高药物释放效率的多功能纳米载体、RNAi的应用、肿瘤细胞凋亡阈值的调控以及克服MDR的物理方法。
Inefficiency in systemic drug delivery and tumor residence as well microenvironmental selection pressures contribute to the development of multidrug resistance (MDR) in cancer. Characteristics of MDR include abnormal vasculature, regions of hypoxia, up-regulation of ABC-transporters, aerobic glycolysis, and an elevated apoptotic threshold. Nano-sized delivery vehicles are ideal for treating MDR cancer as they can improve the therapeutic index of drugs and they can be engineered to achieve multifunctional parameters. The multifunctional ability of nanocarriers makes them more adept at treating heterogeneous tumor mass than traditional chemotherapy. Nanocarriers also have preferential tumor accumulation via the EPR effect; this accumulation can be further enhanced by actively targeting the biological profile of MDR cells. Perhaps the most significant benefit of using nanocarrier drug delivery to treat MDR cancer is that nanocarrier delivery diverts the effects of ABC-transporter mediated drug efflux; which is the primary mechanism of MDR. This review discusses the capabilities, applications, and examples of multifunctional nanocarriers for the treatment of MDR. This review emphasizes multifunctional nanocarriers that enhance drug delivery efficiency, the application of RNAi, modulation of the tumor apoptotic threshold, and physical approaches to overcome MDR.
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DOI：
10.1080/10258140290033066
发表时间：
2002-10-01
期刊：
Journal of biochemistry, molecular biology, and biophysics : JBMBB : the official journal of the Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB)
影响因子：
--
作者：
Gaber, Mohamed H
通讯作者：
Gaber, Mohamed H
DOI：
10.1016/j.bbamcr.2007.12.006
发表时间：
2008-03-01
影响因子：
5.1
作者：
Depping, Reinhard;Steinhoff, Amrei;Koehler, Matthias
通讯作者：
Koehler, Matthias
影响因子：
11.5
作者：
Devalapally, Harikrishna;Duan, Zhenfeng;Amiji, Mansoor M.
通讯作者：
Amiji, Mansoor M.
影响因子：
3.7
作者：
Buys, Timon P. H.;Chari, Raj;Ling, Victor
通讯作者：
Ling, Victor
影响因子：
6.7
作者：
Chinn, L. W.;Kroetz, D. L.
通讯作者：
Kroetz, D. L.