Jabr-Milane Lara S, van Vlerken Lilian E, Yadav Sunita, Amiji Mansoor M
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, MA 02115, USA.
Cancer Treat Rev. 2008 Nov;34(7):592-602. doi: 10.1016/j.ctrv.2008.04.003. Epub 2008 Jun 5.
The development of resistance to variety of chemotherapeutic agents is one of the major challenges in effective cancer treatment. Tumor cells are able to generate a multi-drug resistance (MDR) phenotype due to microenvironmental selection pressures. This review addresses the use of nanotechnology-based delivery systems to overcome MDR in solid tumors. Our own work along with evidence from the literature illustrates the development of various types of engineered nanocarriers specifically designed to enhance tumor-targeted delivery through passive and active targeting strategies. Additionally, multi-functional nanocarriers are developed to enhance drug delivery and overcome MDR by either simultaneous or sequential delivery of resistance modulators (e.g., with P-glycoprotein substrates), agents that regulate intracellular pH, agents that lower the apoptotic threshold (e.g., with ceramide), or in combination with energy delivery (e.g., sound, heat, and light) to enhance the effectiveness of anticancer agents in refractory tumors. In preclinical studies, the use of multi-functional nanocarriers has shown significant promise in enhancing cancer therapy, especially against MDR tumors.
对多种化疗药物产生耐药性是有效治疗癌症的主要挑战之一。由于微环境选择压力，肿瘤细胞能够产生多药耐药（MDR）表型。本综述探讨了基于纳米技术的递送系统在克服实体瘤多药耐药方面的应用。我们自己的研究以及文献证据表明，通过被动和主动靶向策略，已开发出各种类型的工程纳米载体，专门用于增强肿瘤靶向递送。此外，还开发了多功能纳米载体，通过同时或顺序递送耐药调节剂（如P-糖蛋白底物）、调节细胞内pH值的试剂、降低凋亡阈值的试剂（如神经酰胺）或与能量递送（如声、热和光）相结合，来增强药物递送并克服多药耐药，从而提高难治性肿瘤中抗癌药物的疗效。在临床前研究中，多功能纳米载体在增强癌症治疗，尤其是对抗多药耐药肿瘤方面已显示出巨大的前景。
