ATP-responsive copper()-doped ZIF-nanoparticles for synergistic cancer therapy: combining cuproptosis and chemo/chemodynamic therapy

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-11, Vol.12 (44), p.11414-11425
• Main Authors: Deng, Wei-Qun, Chen, Jun-Tao, Chen, Si-Si, Wang, Zhi-Qing, Mao, Guo-Jiang, Hu, Liufang, Ouyang, Juan, Li, Chun-Yan
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - chemistry; Adenosine Triphosphate - metabolism; Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; ATP; Cancer; Cancer therapies; Cell Proliferation - drug effects; Chemotherapy; Copper; Copper - chemistry; Copper - pharmacology; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Screening Assays, Antitumor; Female; Global health; Glutathione; Humans; Hydrogen peroxide; Mice; Mice, Inbred BALB C; Nanoparticles; Nanoparticles - chemistry; Particle Size; Public health; Tumors; Zeolites - chemistry; Zeolites - pharmacology
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d4tb01574f

Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu 2+ -DOX@ZIF-90 is designed by incorporating copper( ii ) (Cu( ii )) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu 2+ -DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu( ii ). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu( ii ) interacts with glutathione (GSH) to generate Cu( i ), catalyzing H 2 O 2 to produce &z.rad;OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu( ii ) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. In vivo experimental findings demonstrate that Cu 2+ -DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer. Cu 2+ -DOX@ZIF-90 nanoparticles exploit elevated ATP levels in cancer cells for synergistic chemotherapy, chemodynamic therapy and cuproptosis, demonstrating effective tumor inhibition without causing damage to normal tissues and organs.