Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles.

Abstract

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.

• Authors: Hongzhi Qiao, Lei Zhang, Dong Fang, Zhenzhu Zhu, Weijiang He, Lihong Hu, Liuqing Di, Zijian Guo, Xiaoyong Wang
• Journal: Chemical science (Chem Sci) Vol. 12 Issue 12 Pg. 4547-4556 (Feb 09 2021) ISSN: 2041-6520 [Print] England
• PMID: 34163720 (Publication Type: Journal Article)
• Copyright: This journal is © The Royal Society of Chemistry.