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

Abstract

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. STATEMENT OF SIGNIFICANCE: 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.