2. Academic Validation
  3. Microorganism-enabled photosynthetic oxygeneration and ferroptosis induction reshape tumor microenvironment for augmented nanodynamic therapy

Microorganism-enabled photosynthetic oxygeneration and ferroptosis induction reshape tumor microenvironment for augmented nanodynamic therapy

  • Biomaterials. 2022 Jul 21;287:121688. doi: 10.1016/j.biomaterials.2022.121688.
Shuting Lu 1,  Wei Feng 2,  Xijuan Yao 1,  Xinran Song 3,  Jinhe Guo 4,  Yu Chen 5,  Zhongqian Hu 6
Affiliations

Affiliations

  • 1 Center of Interventional Radiology and Vascular Surgery, Department of Radiology and Ultrasound, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China.
  • 2 Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China. Electronic address: [email protected].
  • 3 Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Tongji University Cancer Center, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Tongji University School of Medicine, Shanghai, 200072, PR China.
  • 4 Center of Interventional Radiology and Vascular Surgery, Department of Radiology and Ultrasound, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China. Electronic address: [email protected].
  • 5 Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China. Electronic address: [email protected].
  • 6 Center of Interventional Radiology and Vascular Surgery, Department of Radiology and Ultrasound, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China. Electronic address: [email protected].
PMID: 35926358 DOI: 10.1016/j.biomaterials.2022.121688
Abstract

Nanodynamic therapy (NDT) based on Reactive Oxygen Species (ROS) generation has been envisioned as a distinct modality for efficient Cancer treatment. However, insufficient ROS generation and partial ROS consumption frequently limit the theraputic effect and outcome of NDT owing to the low oxygen (O2) tension and high glutathione (GSH) level in tumor microenvironment (TME). To circumvent these critical issues, we herein proposed and engineered the biodegradable GSH-depletion Mn(III)-riched manganese oxide nanospikes (MnOx NSs) with the photosynthetic Bacterial cyanobacteria (Cyan) as a high-efficient and synergistic platform to reshape TME by simultaneously increasing oxygen content and decreasing GSH level. Specifically, under the trigger of acidity, MnOx NSs reacted with photosynthetic oxygen can generate toxic singlet oxygen (1O2). Moreover, MnOx NSs significantly reduced intracellular GSH, resulting in decreased GPX4 activity, which induced tumor cell non-apoptotic Ferroptosis. Consequently, this combined strategy based on coadministration with Cyan and MnOx NSs demonstrated the superior antitumor efficacy via amplification of oxidative stress in 4T1 tumor-bearing mice for the synergetic oxygen-augmented nanodynamic/Ferroptosis therapy. This work highlights a facile synergistic micro-/nano-system with the specific capability of reshaping TME to augment the sensitivity and therapeutic efficacy of NDT in solid hypoxic tumor therapy.

Keywords

Cyanobacteria; Ferroptosis; Manganese oxide nanospikes; Nanodynamic therapy; Photosynthesis.

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