中国医学科学院学报

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中国医学科学院学报

中国医学科学院学报 ›› 2021, Vol. 43 ›› Issue (4): 620-627.doi: 10.3881/j.issn.1000-503X.12828

• 综述 • 上一篇    下一篇

多功能纳米粒干预肿瘤细胞膜转运蛋白相关性耐药的研究进展

江唯希1,2,任建丽1,2()   

  1. 1重庆医科大学超声影像学研究所超声分子影像重庆市重点实验室,重庆 400016
    2重庆医科大学附属第二医院超声科,重庆 400016
  • 收稿日期:2020-04-08 出版日期:2021-08-30 发布日期:2021-09-03
  • 通讯作者: 任建丽 E-mail:renjianli@cqmu.edu.cn
  • 基金资助:
    国家自然科学基金(81873901);重庆市自然科学基金重点项目(cstc2019jcyj-zdxmX0020);宽仁骨干人才项目(KR2019G001)

Progression on Multifunctional Nanoparticles Interfering with Cell Membrane Transporters-associated Drug Resistance

JIANG Weixi1,2,REN Jianli1,2()   

  1. 1Chongqing Key Laboratory of Ultrasound Molecular Imaging,Institute of Ultrasound Imaging, Chongqing Medical University,Chongqing 400016,China
    2Department of Ultrasound,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China
  • Received:2020-04-08 Published:2021-08-30 Online:2021-09-03
  • Contact: REN Jianli E-mail:renjianli@cqmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(81873901);Key Project of Natural Science Foundation of Chongqing(cstc2019jcyj-zdxmX0020);Talents Project of Kuanren(KR2019G001)

摘要:

肿瘤多药耐药(MDR)是指肿瘤细胞在多种机制的介导下,失去对传统化疗药物的敏感性,导致化疗疗效降低。研究认为,包括细胞膜转运蛋白介导的药物外排、肿瘤组织中特殊的微环境、细胞DNA自我修复及抗凋亡、上皮-间质细胞转化等在内的多种因素均可能是导致MDR形成的原因。细胞膜转运蛋白介导的药物外排是指由于肿瘤细胞膜表面ATP结合盒转运蛋白表达上调,导致经由该通道“泵出”细胞外的抗肿瘤药物量增加,降低细胞中的药物浓度从而形成细胞耐药。采取有效的方法抑制由细胞膜转运蛋白过表达引起的药物外泵可能是逆转MDR的关键。多功能纳米粒子作为一种具有良好的应用前景的药物递送系统,已经在抗肿瘤治疗中呈现出诸多优势。此外,经合理设计的纳米粒子还可以结合多种策略协同化疗克服肿瘤多药耐药。本文详细综述运用多功能纳米给药系统结合不同MDR逆转策略,如药物共递送、外界响应及靶点修饰等干预细胞膜转运蛋白外排作用的相关研究,为纳米给药系统下一步的开发以及逆转手段的制定提供参考。

关键词: 多药耐药, ATP结合盒转运蛋白, P-糖蛋白, 药物递送系统

Abstract:

Multi-drug resistance(MDR)refers to the loss of sensitivity of tumor cells to traditional chemotherapeutics agents under the mediation of various mechanisms,resulting in the reduction of chemotherapy efficacy.Current studies suggest that a variety of factors,including cell membrane transporter-mediated efflux of anti-tumor drugs,special microenvironment in tumor tissue,DNA self-repair and anti-apoptotic process,and epithelial-mesenchymal cell transformation,may contribute to the formation of MDR.Cell membrane transporter-mediated drug efflux refers to an increase in the amount of anti-tumor drug pumped out of the cell through the up-regulation of the ATP-binding cassette transporter on tumor cell membrane,which reduces the concentration of the drug in the cell,thus forming MDR.An effective method to inhibit the efflux pump caused by overexpression of membrane transporters plays an important role in overcoming MDR.As a promising drug delivery system,multifunctional nanoparticles have demonstrated many advantages in antitumor therapy.Meanwhile,nanoparticles with tailored design are capable of overcoming MDR when combined with a variety of strategies.This paper described in detail the studies relevant to the use of multifunctional nano-sized drug delivery system combined with different strategies,such as co-delivery of agents,external responsiveness or target modification for intervention with efflux pump in order to reverse MDR.This paper provides reference for the development of nano-sized drug delivery system and the formulation of reversal strategy in the future.

Key words: multidrug resistance, ATP-binding cassette transporters, P-glycoprotein, drug delivery system

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