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用于应对多药耐药中癌细胞生物学的纳米医学

Nanomedicine to Deal With Cancer Cell Biology in Multi-Drug Resistance.

作者信息

Tekchandani Pawan, Kurmi Balak Das, Paliwal Shivani Rai

机构信息

Pharmaceutics Research Laboratory, Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur-495 009, India.

出版信息

Mini Rev Med Chem. 2017;17(18):1793-1810. doi: 10.2174/1389557516666160219123222.

Abstract

Today Cancer still remains a major cause of mortality and death worldwide, in humans. Chemotherapy, a key treatment strategy in cancer, has significant hurdles such as the occurrence of chemoresistance in cancer, which is inherent unresponsiveness or acquired upon exposure to chemotherapeutics. The resistance of cancer cells to an antineoplastic agent accompanied to other chemotherapeutic drugs with different structures and mechanisms of action called multi-drug resistance (MDR) plays an important role in the failure of chemo- therapeutics. MDR is primarily based on the overexpression of drug efflux pumps in the cellular membrane, which belongs to the ATP-binding cassette (ABC) superfamily of proteins, are P-gp (P-glycoprotein) and multidrug resistance-associated protein (MRP). Over the years, various strategies have been evaluated to overcome MDR, based not only on the use of MDR modulators but also on the implementation an innovative approach and advanced nanosized drug delivery systems. Nanomedicine is an emerging tool of chemotherapy that focuses on alternative drug delivery for improvement of the treatment efficacy and reducing side effects to normal tissues. This review aims to focus on the details biology, reversal strategies option with the limitation of MDR and various advantages of the present medical science nanotechnology with intracellular delivery aspects for overcoming the significant potential for improving the treatment of MDR malignancies.

摘要

如今,癌症仍是全球人类死亡的主要原因。化疗作为癌症治疗的关键策略,存在诸多重大障碍,比如癌症中会出现化疗耐药性,这表现为内在的无反应性或在接触化疗药物后产生的耐药性。癌细胞对一种抗肿瘤药物产生耐药性,同时对其他结构和作用机制不同的化疗药物也产生耐药性,这种情况被称为多药耐药性(MDR),它在化疗失败中起着重要作用。MDR主要基于细胞膜上药物外排泵的过度表达,这些外排泵属于ATP结合盒(ABC)蛋白超家族,包括P - 糖蛋白(P - gp)和多药耐药相关蛋白(MRP)。多年来,人们评估了各种克服MDR的策略,不仅基于使用MDR调节剂,还基于采用创新方法和先进的纳米级药物递送系统。纳米医学是一种新兴的化疗工具,专注于替代药物递送,以提高治疗效果并减少对正常组织的副作用。本综述旨在聚焦于MDR的详细生物学机制、逆转策略选择及其局限性,以及当前医学科学纳米技术在细胞内递送方面的各种优势,以克服改善MDR恶性肿瘤治疗的重大潜力。

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