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多功能纳米颗粒干预细胞膜转运蛋白相关耐药性的研究进展

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

作者信息

Jiang Wei-Xi, Ren Jian-Li

机构信息

Chongqing Key Laboratory of Ultrasound Molecular Imaging,Institute of Ultrasound Imaging, Chongqing Medical University,Chongqing 400016,China.

Department of Ultrasound,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China.

出版信息

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2021 Aug;43(4):620-627. doi: 10.3881/j.issn.1000-503X.12828.

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.

摘要

多药耐药(MDR)是指肿瘤细胞在多种机制介导下对传统化疗药物失去敏感性,导致化疗疗效降低。目前研究表明,包括细胞膜转运蛋白介导的抗肿瘤药物外排、肿瘤组织中的特殊微环境、DNA自我修复和抗凋亡过程以及上皮-间质细胞转化等多种因素可能促成多药耐药的形成。细胞膜转运蛋白介导的药物外排是指通过肿瘤细胞膜上ATP结合盒转运蛋白的上调,使细胞排出的抗肿瘤药物量增加,从而降低细胞内药物浓度,进而形成多药耐药。抑制由膜转运蛋白过表达引起的外排泵的有效方法在克服多药耐药中起着重要作用。作为一种有前景的药物递送系统,多功能纳米粒子在抗肿瘤治疗中已展现出诸多优势。同时,经过定制设计的纳米粒子与多种策略联合时能够克服多药耐药。本文详细描述了与使用多功能纳米级药物递送系统结合不同策略(如联合递送药物、外部响应性或靶向修饰以干预外排泵从而逆转多药耐药)相关的研究。本文为未来纳米级药物递送系统的开发及逆转策略的制定提供参考。

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