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氧化还原响应性纳米载体作为肿瘤靶向药物传递系统。

Redox-responsive nano-carriers as tumor-targeted drug delivery systems.

机构信息

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

出版信息

Eur J Med Chem. 2018 Sep 5;157:705-715. doi: 10.1016/j.ejmech.2018.08.034. Epub 2018 Aug 13.

Abstract

With ever increasing scientific knowledge and awareness, research is underway around the globe to design new types of stimuli (external/internal) responsive nano-carriers for biotechnological applications at large and biomedical/pharmaceutical in particular. Based on literature evidence, stimuli-responsive carriers have been classified into four major categories, i.e. (1) physical, (2) chemical, (3) biological, and (4) dual (combination of any of the first three classes). Among various types, redox-responsive nano-carriers are of supreme interests and discussed here in this review. The difference in redox potential in tumor and normal tissue is considered as a potential target for tumor targeting leading to the development of redox-responsive drug delivery systems (DDS). In this regard, a high concentration of glutathione in tumor/intracellular environment has extensively been exploited. Disulfide bonds were found as a promising tool for designing redox-responsive which tend to cleave in a reductive environment forming sulfhydryl groups. Many nano-carriers have been explored widely to control tumor growth. These systems were used against the tumor xenograft animal model and showed improved tumor targeting with tumor growth inhibition. Herein, an effort has been made to summarize various aspects from design to development of numerous types of redox-responsive DDS including liposomes, micelles, nanoparticles, nanogel and prodrug based nanomedicines. An emphasis is also given on various types of nano-carriers with special reference to the tumor-targeted drug delivery applications. Also, dual responsive nano-carriers (in addition to redox-responsive) have also been briefly discussed. Towards the end of the chapter, the information is also given on their future perspectives.

摘要

随着科学知识和意识的不断提高,全球范围内正在进行研究,以设计用于生物技术应用(尤其是生物医学/制药)的新型刺激(外部/内部)响应型纳米载体。根据文献证据,刺激响应载体已被分为四大类,即(1)物理,(2)化学,(3)生物和(4)双重(前三种类型的任意组合)。在各种类型中,氧化还原响应型纳米载体是最受关注的,并在本文中进行了讨论。肿瘤和正常组织之间氧化还原电位的差异被认为是肿瘤靶向的潜在目标,从而导致氧化还原响应型药物传递系统(DDS)的发展。在这方面,肿瘤/细胞内环境中高浓度的谷胱甘肽已被广泛利用。二硫键被发现是设计氧化还原响应的有前途的工具,它倾向于在还原环境中裂解形成巯基。已经广泛探索了许多纳米载体来控制肿瘤生长。这些系统被用于肿瘤异种移植动物模型,并显示出改善的肿瘤靶向和肿瘤生长抑制。本文努力从设计到开发各种类型的氧化还原响应型 DDS (包括脂质体、胶束、纳米颗粒、纳米凝胶和前药纳米药物)方面进行总结。还特别强调了各种类型的纳米载体,特别参考了肿瘤靶向药物传递应用。此外,还简要讨论了双重响应纳米载体(除了氧化还原响应)。在本章的最后,还提供了有关它们未来前景的信息。

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