DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy
Chemo-dynamic therapy (CDT) has a great potential in tumor extirpation. It entails producing hypertoxic reactive oxygen species (ROS) that damage the DNA of tumor cells and other biomacromolecules. However, the efficiency of CDT is severely hampered by the massive presence of glutathione (GSH) in tu...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2025-03-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24004936 |
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| author | Cui Ren Zhiyong Shi Xiaowen Zhang Xueer Yu Yang Gao Zhi Qi Yu Chen Yong Wang |
| author_facet | Cui Ren Zhiyong Shi Xiaowen Zhang Xueer Yu Yang Gao Zhi Qi Yu Chen Yong Wang |
| author_sort | Cui Ren |
| collection | DOAJ |
| description | Chemo-dynamic therapy (CDT) has a great potential in tumor extirpation. It entails producing hypertoxic reactive oxygen species (ROS) that damage the DNA of tumor cells and other biomacromolecules. However, the efficiency of CDT is severely hampered by the massive presence of glutathione (GSH) in tumor cells and the interference of ROS defense systems, such as Mutt homolog 1 (MTH1) protein sanitizes ROS-oxidized nucleotide pools. In this research, DNA-mediated self-assembly nanoparticles (HTCG@TA NPs) were engineered with high-performance amplified oxidative damage and gene therapy effect for synergistic anti-tumor treatment. Cu2+ was converted into Cu + by redox reactions to deplete GSH while H2O2 was catalyzed to generate hydroxyl radicals (·OH). As a result, the ROS level was evidently improved. Moreover, controllable-released TH588 prevented MTH1-mediated DNA repairing, thus aggravated oxidative damage to tumor cells. Meanwhile, the released functional nucleic acid G3139 downregulated the expression of Bcl-2, and accelerated the apoptosis of tumor cells. In conclusion, the HTCG@TA demonstrated significant effect in oxidative damage amplification and tumor inhibition both in vitro and in vivo, which has provided a new outlook for the clinical application of chemo-dynamic tumor treatment and synergistic gene therapy with self-delivery nanoplatforms. |
| format | Article |
| id | doaj-art-4d38775086614db5b81b131655587eb0 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-4d38775086614db5b81b131655587eb02025-01-26T05:04:20ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-03-0145434445DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapyCui Ren0Zhiyong Shi1Xiaowen Zhang2Xueer Yu3Yang Gao4Zhi Qi5Yu Chen6Yong Wang7Department of Chemistry, School of Science, Tianjin University, Tianjin, 300072, ChinaDepartment of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, ChinaDepartment of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, ChinaSchool of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, ChinaDepartment of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China; Corresponding author.Department of Molecular Pharmacology, School of Medicine, Nankai University, Tianjin, 300071, China; Corresponding author.Department of Chemistry, School of Science, Tianjin University, Tianjin, 300072, China; Corresponding author.Department of Chemistry, School of Science, Tianjin University, Tianjin, 300072, ChinaChemo-dynamic therapy (CDT) has a great potential in tumor extirpation. It entails producing hypertoxic reactive oxygen species (ROS) that damage the DNA of tumor cells and other biomacromolecules. However, the efficiency of CDT is severely hampered by the massive presence of glutathione (GSH) in tumor cells and the interference of ROS defense systems, such as Mutt homolog 1 (MTH1) protein sanitizes ROS-oxidized nucleotide pools. In this research, DNA-mediated self-assembly nanoparticles (HTCG@TA NPs) were engineered with high-performance amplified oxidative damage and gene therapy effect for synergistic anti-tumor treatment. Cu2+ was converted into Cu + by redox reactions to deplete GSH while H2O2 was catalyzed to generate hydroxyl radicals (·OH). As a result, the ROS level was evidently improved. Moreover, controllable-released TH588 prevented MTH1-mediated DNA repairing, thus aggravated oxidative damage to tumor cells. Meanwhile, the released functional nucleic acid G3139 downregulated the expression of Bcl-2, and accelerated the apoptosis of tumor cells. In conclusion, the HTCG@TA demonstrated significant effect in oxidative damage amplification and tumor inhibition both in vitro and in vivo, which has provided a new outlook for the clinical application of chemo-dynamic tumor treatment and synergistic gene therapy with self-delivery nanoplatforms.http://www.sciencedirect.com/science/article/pii/S2452199X24004936Chemo-dynamic therapyOxidative damage amplifierG3139MTH1 inhibitorTH588Cancer therapy |
| spellingShingle | Cui Ren Zhiyong Shi Xiaowen Zhang Xueer Yu Yang Gao Zhi Qi Yu Chen Yong Wang DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy Bioactive Materials Chemo-dynamic therapy Oxidative damage amplifier G3139 MTH1 inhibitor TH588 Cancer therapy |
| title | DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy |
| title_full | DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy |
| title_fullStr | DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy |
| title_full_unstemmed | DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy |
| title_short | DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy |
| title_sort | dna mediated self assembly oxidative damage amplifier combined with copper and mth1 inhibitor for cancer therapy |
| topic | Chemo-dynamic therapy Oxidative damage amplifier G3139 MTH1 inhibitor TH588 Cancer therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24004936 |
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