Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles†
| Autor: | Xiaoyong Wang, Lihong Hu, Dong Fang, Zhenzhu Zhu, Hongzhi Qiao, Zijian Guo, Weijiang He, Liuqing Di, Lei Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Small interfering RNA Chemistry 02 engineering and technology General Chemistry Drug resistance 021001 nanoscience & nanotechnology Cell biology 03 medical and health sciences Apoptosis RNA interference Cancer cell Gene silencing 0210 nano-technology Gene Intracellular 030304 developmental biology |
| Zdroj: | Chemical Science |
| ISSN: | 2041-6539 2041-6520 |
| Popis: | Copper complexes are promising anticancer agents widely studied to overcome tumor resistance to metal-based anticancer drugs. Nevertheless, copper complexes per se encounter drug resistance from time to time. Adenosine-5′-triphosphate (ATP)-responsive nanoparticles containing a copper complex CTND and B-cell lymphoma 2 (Bcl-2) small interfering RNA (siRNA) were constructed to cope with the resistance of cancer cells to the complex. CTND and siRNA can be released from the nanoparticles in cancer cells upon reacting with intracellular ATP. The resistance of B16F10 melanoma cells to CTND was terminated by silencing the cellular Bcl-2 gene via RNA interference, and the therapeutic efficacy was significantly enhanced. The nanoparticles triggered a cellular autophagy that amplified the apoptotic signals, thus revealing a novel mechanism for antagonizing the resistance of copper complexes. In view of the extensive association of Bcl-2 protein with cancer resistance to chemotherapeutics, this strategy may be universally applicable for overcoming the ubiquitous drug resistance to metallodrugs. Bcl-2-related tumor resistance to anticancer drugs can be overcome by silencing the cellular Bcl-2 gene via RNA interference. The realization of the goal is exemplified by delivering Bcl-2 siRNA and a tumor-resistant Cu complex to cancer cells with an ATP-responsive nanocarrier. |
| Databáze: | OpenAIRE |
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