Synergistic ferroptosis-gemcitabine chemotherapy of the gemcitabine loaded carbonaceous nanozymes to enhance the treatment and magnetic resonance imaging monitoring of pancreatic cancer

• Published in: Acta biomaterialia Vol. 142; pp. 284 - 297
• Main Authors: Zhang, Gaorui, Li, Nianlu, Qi, Yafei, Zhao, Quanqin, Zhan, Jinhua, Yu, Dexin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2022; Elsevier BV
• Subjects: Adenocarcinoma; Antineoplastic Agents - therapeutic use; Biocompatibility; Cancer; Cell Line, Tumor; Chemotherapy; Deoxycytidine - analogs & derivatives; Ferroptosis; Gemcitabine; Glutathione; Glutathione peroxidase; Glutathione Peroxidase - therapeutic use; Humans; Magnetic permeability; Magnetic Resonance Imaging; Magnetic susceptibility; Medical imaging; Monitoring; Nanoparticles; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Peroxidase; Reactive Oxygen Species; Resonance; Synergetic therapy; Theranostics; Ferroptosis; Magnetic resonance imaging; Theranostics; Pancreatic cancer; Synergetic therapy
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2022.02.006

Pancreatic adenocarcinoma (PDAC) is one of the deadliest cancers, and it is resistant to most conventional antineoplastic therapies. To address this challenge, gemcitabine (Gem)-loaded carbonaceous nanoparticles (MFC-Gem) as nanozymes and a theranostic platform were fabricated and used for MR-guided ferroptosis-chemo synergetic therapy of PDAC. As a biocompatible carrier, MFC-Gem nanoparticles are regarded as peroxidase-like and glutathione peroxidase-like nanozymes that promote ferroptosis therapy by effectively generating ROS and consuming GSH. Meanwhile, the combination of MnFe2O4 and Gem can markedly enhance synergetic therapy by both ferroptosis and Gem chemotherapy. MFC-Gem has higher magnetic susceptibility and was used for simultaneous magnetic resonance imaging (MRI) monitoring of the PDAC treatment. In conclusion, these salient features unequivocally indicate that this biocompatible nanotheranostic system has cooperative and enhancing chemotherapy effects for anti-PDAC therapy with simultaneous MRI monitoring. Pancreatic adenocarcinoma (PDAC) is one of the deadliest cancers, and it is resistant to most conventional antineoplastic therapies. To address this challenge, gemcitabine (Gem)-loaded carbonaceous nanoparticles (MFC-Gem) as nanozymes and a theranostic platform were fabricated and used for MR-guided ferroptosis-chemo synergetic therapy of PDAC. i) MFC nanoparticles are regarded as peroxidase-like and glutathione peroxidase-like nanozymes that enhance ferroptosis therapy by effectively generating ROS and consuming GSH. ii) The combination of MnFe2O4 and Gem can markedly enhance synergetic therapy by both ferroptosis and Gem chemotherapy. iii) MFC-Gem has higher magnetic susceptibility and was used for simultaneous magnetic resonance imaging (MRI) monitoring of the PDAC treatment. [Display omitted]