Zhang Gaorui, Li Nianlu, Qi Yafei, Zhao Quanqin, Zhan Jinhua, Yu Dexin
Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Translational Medicine Research Center in Nano Molecular and Functional Imaging of Shandong University, Jinan, 250100, China.
Key Laboratory for Colloid & Interface Chemistry of Education Ministry, Department of Chemistry, Shandong University, Jinan, 250100, China.
Acta Biomater. 2022 Apr 1;142:284-297. doi: 10.1016/j.actbio.2022.02.006. Epub 2022 Feb 10.
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 MnFeO 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 MnFeO 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.
胰腺腺癌（PDAC）是最致命的癌症之一，并且对大多数传统抗肿瘤疗法具有抗性。为应对这一挑战，制备了负载吉西他滨（Gem）的碳质纳米颗粒（MFC-Gem）作为纳米酶和治疗诊断平台，并将其用于磁共振引导下的胰腺癌铁死亡-化疗协同治疗。作为生物相容性载体，MFC-Gem纳米颗粒被视为类过氧化物酶和类谷胱甘肽过氧化物酶纳米酶，可通过有效产生活性氧（ROS）和消耗谷胱甘肽（GSH）来促进铁死亡治疗。同时，MnFeO与Gem的组合可通过铁死亡和Gem化疗显著增强协同治疗效果。MFC-Gem具有较高的磁化率，用于胰腺癌治疗的同时磁共振成像（MRI）监测。总之，这些显著特征明确表明，这种生物相容性纳米治疗诊断系统在进行MRI监测的同时，对胰腺癌的治疗具有协同增效的化疗作用。重要意义声明：胰腺腺癌（PDAC）是最致命的癌症之一，并且对大多数传统抗肿瘤疗法具有抗性。为应对这一挑战，制备了负载吉西他滨（Gem）的碳质纳米颗粒（MFC-Gem）作为纳米酶和治疗诊断平台，并将其用于磁共振引导下的胰腺癌铁死亡-化疗协同治疗。i）MFC纳米颗粒被视为类过氧化物酶和类谷胱甘肽过氧化物酶纳米酶，可通过有效产生活性氧（ROS）和消耗谷胱甘肽（GSH）来增强铁死亡治疗。ii）MnFeO与Gem的组合可通过铁死亡和Gem化疗显著增强协同治疗效果。iii）MFC-Gem具有较高的磁化率，用于胰腺癌治疗的同时磁共振成像（MRI）监测。
