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用于化学光热疗法诱导线粒体介导的凋亡性细胞死亡的pH和近红外光响应性磁性氧化铁纳米颗粒

pH and NIR-light-responsive magnetic iron oxide nanoparticles for mitochondria-mediated apoptotic cell death induced by chemo-photothermal therapy.

作者信息

Oh Yunok, Je Jae-Young, Moorthy Madhappan Santha, Seo Hansoo, Cho Won Ho

机构信息

Department of Marine-Bio Convergence Science, Pukyong National University, Busan, 48547, Republic of Korea.

Interdisciplinary Program of Biomedical Mechanical & Electrical Engineering, Pukyong National University, Busan 48513, Republic of Korea.

出版信息

Int J Pharm. 2017 Oct 5;531(1):1-13. doi: 10.1016/j.ijpharm.2017.07.014. Epub 2017 Jul 6.

Abstract

Recently, various therapeutic strategies in anticancer drug development are focused to reduce adverse side effects and to enhance the therapeutic efficacy. Mostly, the iron oxide (FeO) nanoparticles have widely been utilized as an efficient drug delivery system towing to their unique properties such as excellent magnetic behavior, considerably low toxicity, easy surface modification and high drug-loading efficacy. In the present study, we synthesized a multifunctional, DMSA coated, water soluble FeO nanoparticles (FeO@DMSA/DOX) for an effective pH and NIR-light triggered delivery of anticancer drug (DOX) in cancer therapy. The combination of photothermal therapy combined with chemotherapy results demonstrated that the synthesized FeO@DMSA/DOX is an excellent candidate for pH- and NIR-light induced phothothermal agent for an effective delivery of anticancer drug (DOX) into the target sub-cellular level into the human breast cancer (MDA-MB-231) cells. Furthermore, the FeO@DMSA/DOX nanoparticles induced an excellent temperature elevation upon NIR light irradiation and controlled DOX release in vitro. The FeO@DMSA/DOX nanoparticles exhibited synergistic effect when combining chemotherapy with photothermal therapy and showed an excellent cell toxicity to MDA-MB-231 cells. In addition, the combined chemo-photothermal therapy of FeO@DMSA/DOX nanoparticles promoted an effective cell death by mitochondrial disruption mediated by ROS generation. Thus, the synthesized FeO@DMSA/DOX nanoparticles could be utilized as potential anticancer agents for breast cancer treatment.

摘要

最近,抗癌药物开发中的各种治疗策略都聚焦于减少不良反应并提高治疗效果。大多数情况下,氧化铁(FeO)纳米颗粒因其独特的性质,如优异的磁性能、相当低的毒性、易于表面修饰和高载药效率,而被广泛用作一种高效的药物递送系统。在本研究中,我们合成了一种多功能的、包覆二巯基丁二酸(DMSA)的水溶性FeO纳米颗粒(FeO@DMSA/DOX),用于在癌症治疗中实现有效pH和近红外光触发的抗癌药物(阿霉素,DOX)递送。光热疗法与化疗相结合的结果表明,合成的FeO@DMSA/DOX是一种优异的pH和近红外光诱导的光热剂候选物,可将抗癌药物(DOX)有效递送至人乳腺癌(MDA-MB-231)细胞的目标亚细胞水平。此外,FeO@DMSA/DOX纳米颗粒在近红外光照射下能引起显著的温度升高,并在体外控制DOX释放。FeO@DMSA/DOX纳米颗粒在化疗与光热疗法联合使用时表现出协同效应,对MDA-MB-231细胞显示出优异的细胞毒性。此外,FeO@DMSA/DOX纳米颗粒的联合化学-光热疗法通过活性氧生成介导的线粒体破坏促进了有效的细胞死亡。因此,合成的FeO@DMSA/DOX纳米颗粒可作为潜在的抗癌剂用于乳腺癌治疗。

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