GLUT1‐Targeting and GSH‐Responsive DOX/L61 Nanodrug Particles for Enhancing MDR Breast Cancer Therapy,Particle & Particle Systems Characterization

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GLUT1‐Targeting and GSH‐Responsive DOX/L61 Nanodrug Particles for Enhancing MDR Breast Cancer Therapy
Particle & Particle Systems Characterization ( IF 2.7 ) Pub Date : 2020-08-16 , DOI: 10.1002/ppsc.202000165
Xin Wang ₁ , Lu Yang ₁ , Qin Fang ₁ , Jiaxi Xu ₁ , Xu Cheng ₁ , Yanbing Xue ₁ , Rupei Tang ₁

Affiliation

Efficient targeting to tumor tissues and subsequent rapid drug release in cancer cells remains a major challenge for nanodrug delivery systems. Herein, smart nanodrug particles with reduction‐sensitive and active tumor‐targeting ability are constructed based on the nanoprecipitation of glucosamine‐grafted pluronic L61 (GA‐L61) and disulphide‐linked doxorubicin dimer (DOXSSDOX) to overcome tumor multidrug resistance (MDR). These nanoparticles show proper size and excellent stability under neutral conditions, while quickly release DOX due to the breakage of disulfide bonds under reductive medium. In vitro cellular uptake and drug efflux demonstrate that L61 can efficiently increase DOX concentration in MCF/ADR resistant cells by inhibiting the function of drug resistance proteins. In vivo biodistribution reveals that glucose transporter 1 (GLUT1)‐mediated tumor‐targeting significantly improves tumor accumulation of the glucosamine‐contained nanoparticles. Finally, the combination of GLUT1‐targeting, glutathione (GSH)‐responsive, and MDR‐reversal effects in nanoparticles achieve superior antitumor effects, which can provide an efficient, safe, and economic approach for drug delivery and cancer chemotherapy.

中文翻译：

GLUT1靶向和GSH反应性DOX / L61纳米药物颗粒可增强MDR乳腺癌治疗

有效靶向肿瘤组织并随后在癌细胞中快速释放药物仍然是纳米药物递送系统的主要挑战。在本文中，与还原敏感的和活性肿瘤靶向能力是基于葡糖胺接枝普朗尼克L61（GA-L61）和的纳米沉淀构造智能纳米药物颗粒二硫键连接的阿霉素二聚物（DOX  SS DOX）以克服肿瘤的多药耐药性（MDR）。这些纳米粒子在中性条件下显示合适的尺寸和出色的稳定性，同时由于还原性介质中二硫键的断裂而迅速释放DOX。体外细胞吸收和药物外排表明，L61可以通过抑制耐药蛋白的功能来有效增加MCF / ADR耐药细胞中的DOX浓度。体内生物分布显示，葡萄糖转运蛋白1（GLUT1）介导的肿瘤靶向显着改善了含氨基葡萄糖的纳米颗粒的肿瘤蓄积。最后，在纳米颗粒中结合GLUT1靶向，谷胱甘肽（GSH）响应和MDR逆转作用的组合可实现卓越的抗肿瘤作用，从而可以为药物输送和癌症化疗提供有效，安全和经济的方法。

更新日期：2020-09-16

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