Building of CuO<sub>2</sub>@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells
<b>Background/Objectives:</b> With the increase of reactive oxygen species (ROS) production, cancer cells can avoid cell death and damage by up-regulating antioxidant programs. Therefore, it will be more effective to induce cell death by using targeted strategies to further improve ROS l...
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2024-12-01
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| author | Jiaru Zhang Zuoping Li Zhenzhen Xie Shiwan You Yanbing Chen Yuling Zhang Jing Zhang Na Zhao Xiling Deng Shiguo Sun |
| author_facet | Jiaru Zhang Zuoping Li Zhenzhen Xie Shiwan You Yanbing Chen Yuling Zhang Jing Zhang Na Zhao Xiling Deng Shiguo Sun |
| author_sort | Jiaru Zhang |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> With the increase of reactive oxygen species (ROS) production, cancer cells can avoid cell death and damage by up-regulating antioxidant programs. Therefore, it will be more effective to induce cell death by using targeted strategies to further improve ROS levels and drugs that inhibit antioxidant programs. <b>Methods:</b> Considering that dihydroartemisinin (DHA) can cause oxidative damage to protein, DNA, or lipids by producing excessive ROS, while, disulfiram (DSF) can inhibit glutathione (GSH) levels and achieve the therapeutic effect by inhibiting antioxidant system and amplifying oxidative stress, they were co-loaded onto the copper peroxide nanoparticles (CuO<sub>2</sub>) coated with copper tannic acid (Cu-TA), to build a drug delivery system of CuO<sub>2</sub>@Cu-TA@DSF/DHA nanoparticles (CCTDD NPs). In response to the tumor microenvironment, DHA interacts with copper ion (Cu<sup>2+</sup>) to produce ROS, and a double (diethylthiocarbamate)-copper (II) (CuET) is generated by the complexation of DSF and Cu<sup>2+</sup>, which consumes GSH and inhibits antioxidant system. Meanwhile, utilizing the Fenton-like effect induced by the multi-copper mode can achieve ROS storm, activate the MAPK pathway, and achieve chemotherapy (CT) and chemodynamic (CDT). <b>Results:</b> Taking pancreatic cancer cell lines PANC-1 and BxPC-3 as the research objects, cell line experiments in vitro proved that CCTDD NPs exhibit efficient cytotoxicity on cancer cells. <b>Conclusions:</b> The CCTDD NPs show great potential in resisting pancreatic cancer cells and provides a simple strategy for designing powerful metal matrix composites. |
| format | Article |
| id | doaj-art-618d48f07a1a4d37afec61c6f2026122 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-618d48f07a1a4d37afec61c6f20261222024-12-27T14:46:41ZengMDPI AGPharmaceutics1999-49232024-12-011612161410.3390/pharmaceutics16121614Building of CuO<sub>2</sub>@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer CellsJiaru Zhang0Zuoping Li1Zhenzhen Xie2Shiwan You3Yanbing Chen4Yuling Zhang5Jing Zhang6Na Zhao7Xiling Deng8Shiguo Sun9Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832003, China<b>Background/Objectives:</b> With the increase of reactive oxygen species (ROS) production, cancer cells can avoid cell death and damage by up-regulating antioxidant programs. Therefore, it will be more effective to induce cell death by using targeted strategies to further improve ROS levels and drugs that inhibit antioxidant programs. <b>Methods:</b> Considering that dihydroartemisinin (DHA) can cause oxidative damage to protein, DNA, or lipids by producing excessive ROS, while, disulfiram (DSF) can inhibit glutathione (GSH) levels and achieve the therapeutic effect by inhibiting antioxidant system and amplifying oxidative stress, they were co-loaded onto the copper peroxide nanoparticles (CuO<sub>2</sub>) coated with copper tannic acid (Cu-TA), to build a drug delivery system of CuO<sub>2</sub>@Cu-TA@DSF/DHA nanoparticles (CCTDD NPs). In response to the tumor microenvironment, DHA interacts with copper ion (Cu<sup>2+</sup>) to produce ROS, and a double (diethylthiocarbamate)-copper (II) (CuET) is generated by the complexation of DSF and Cu<sup>2+</sup>, which consumes GSH and inhibits antioxidant system. Meanwhile, utilizing the Fenton-like effect induced by the multi-copper mode can achieve ROS storm, activate the MAPK pathway, and achieve chemotherapy (CT) and chemodynamic (CDT). <b>Results:</b> Taking pancreatic cancer cell lines PANC-1 and BxPC-3 as the research objects, cell line experiments in vitro proved that CCTDD NPs exhibit efficient cytotoxicity on cancer cells. <b>Conclusions:</b> The CCTDD NPs show great potential in resisting pancreatic cancer cells and provides a simple strategy for designing powerful metal matrix composites.https://www.mdpi.com/1999-4923/16/12/1614dihydroartemisinindisulfiramchemotherapychemodynamicsynergetic therapy |
| spellingShingle | Jiaru Zhang Zuoping Li Zhenzhen Xie Shiwan You Yanbing Chen Yuling Zhang Jing Zhang Na Zhao Xiling Deng Shiguo Sun Building of CuO<sub>2</sub>@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells Pharmaceutics dihydroartemisinin disulfiram chemotherapy chemodynamic synergetic therapy |
| title | Building of CuO<sub>2</sub>@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells |
| title_full | Building of CuO<sub>2</sub>@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells |
| title_fullStr | Building of CuO<sub>2</sub>@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells |
| title_full_unstemmed | Building of CuO<sub>2</sub>@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells |
| title_short | Building of CuO<sub>2</sub>@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells |
| title_sort | building of cuo sub 2 sub cu ta dsf dha nanoparticle targets mapk pathway to achieve synergetic chemotherapy and chemodynamic for pancreatic cancer cells |
| topic | dihydroartemisinin disulfiram chemotherapy chemodynamic synergetic therapy |
| url | https://www.mdpi.com/1999-4923/16/12/1614 |
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