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基于端粒酶触发的光动力治疗与基因沉默协同效应的智能纳米器件用于精确的癌细胞治疗。

An intelligent nanodevice based on the synergistic effect of telomerase-triggered photodynamic therapy and gene-silencing for precise cancer cell therapy.

机构信息

Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China.

出版信息

Nanoscale. 2020 May 14;12(18):10380-10389. doi: 10.1039/d0nr02096f.

Abstract

The development of intelligent and precise cancer therapy systems that enable accurate diagnosis and specific elimination of cancer cells while protecting normal cells to improve the safety and effectiveness of the treatment is still a challenge. Herein, we report a novel activatable nanodevice for precise cancer therapy. The nanodevice is constructed by adsorbing a DNA duplex probe onto MnO2 nanosheets. After cellular uptake, the DNA duplex probe undergoes telomerase-triggered conformation switching, resulting in a Ce6 "turn-on" signal for the identification of cancer cells. Furthermore, Deoxyribozyme (DNAzyme) is activated to catalyse the cleavage of survivin mRNA, actualizing a precise synergistic therapy in cancer cells involving photodynamic therapy and gene-silencing. The MnO2 nanosheets provide Mn2+ for the DNAzyme and relieve hypoxia to improve the efficiency of the photodynamic therapy. Live cell studies reveal that this nanodevice can diagnose cancer cells and specifically eliminate them without harming normal cells, so making the treatment safer and more effective. The developed DNA-MnO2 nanodevice provides a valuable and general platform for precise cancer therapy.

摘要

开发智能精准的癌症治疗系统,实现对癌细胞的精确诊断和特异性消除,同时保护正常细胞,以提高治疗的安全性和有效性,仍然是一个挑战。在此,我们报告了一种用于精确癌症治疗的新型可激活纳米器件。该纳米器件通过将 DNA 双链探针吸附到 MnO2 纳米片上构建而成。在细胞摄取后,DNA 双链探针经历端粒酶触发的构象转换,导致 Ce6“开启”信号,用于识别癌细胞。此外,脱氧核酶(DNAzyme)被激活以催化survivin mRNA 的切割,在癌细胞中实现精确的协同治疗,包括光动力治疗和基因沉默。MnO2 纳米片为 DNAzyme 提供 Mn2+并缓解缺氧,以提高光动力治疗的效率。活细胞研究表明,这种纳米器件可以诊断癌细胞并特异性地消除它们,而不会伤害正常细胞,从而使治疗更安全、更有效。所开发的 DNA-MnO2 纳米器件为精确癌症治疗提供了一个有价值且通用的平台。

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