biostudies-literatureQiao HNational Basic Research Program of ChinaPostdoctoral Science Foundation of Jiangsu ProvinceNational Natural Science Foundation of ChinaChina Postdoctoral Science FoundationQinglan Project of Jiangsu Province of ChinaSix Talent Peaks Project in Jiangsu ProvinceChina Association for Science and Technology4547-4556https://www.ebi.ac.uk/biostudies/studies/S-EPMC8179575biostudies-literatureUnknown12(12)Copper complexes are promising anticancer agents widely studied to overcome tumor resistance to metal-based anticancer drugs. Nevertheless, copper complexes <i>per se</i> 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 <i>via</i> RNA interference, and the therapeutic efficacy was significantly enhanced. The nanoparticles triggered a cellular autophagy that amplifiedChemical scienceSurmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles.PMC81795752015CB8563002017QNRC001SWYY-0572016M59181321877059315708091601238CDi LQiao HZhu ZGuo ZFang DHe WZhang LHu LWang XfalseSurmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles.Copper complexes are promising anticancer agents widely studied to overcome tumor resistance to metal-based anticancer drugs. Nevertheless, copper complexes <i>per se</i> 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 <i>via</i> RNA interference, and the therapeutic efficacy was significantly enhanced. The nanoparticles triggered a cellular autophagy that amplified2021-01-01T00:00:00Z2021 Feb2026-05-08T19:01:23.006Z2022-02-10T16:11:20.201ZS-EPMC81795753416372010.1039/d0sc06680j