Theranostics 2021; 11(15):7439-7449. doi:10.7150/thno.62437
Mn3+-rich oxide/persistent luminescence nanoparticles achieve light-free generation of singlet oxygen and hydroxyl radicals for responsive imaging and tumor treatment
1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
2. Department of Radiation Oncology, Cancer Center, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
3. Departments of Diagnostic Radiology and Surgery, Clinical Imaging Research Centre, Centre for Translational Medicine, Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, Departments of Chemical and Biomolecular Engineering, and Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore.
Ding D, Feng Y, Qin R, Li S, Chen L, Jing J, Zhang C, Sun W, Li Y, Chen X, Chen H. Mn3+-rich oxide/persistent luminescence nanoparticles achieve light-free generation of singlet oxygen and hydroxyl radicals for responsive imaging and tumor treatment. Theranostics 2021; 11(15):7439-7449. doi:10.7150/thno.62437. Available from https://www.thno.org/v11p7439.htm
X-ray excited persistent luminescence (XEPL) imaging has attracted increasing attention in biomedical imaging due to elimination of autofluorescence, high signal-to-noise ratio and repeatable activation with high penetration. However, optical imaging still suffers from limited for high spatial resolution.
Methods: Herein, we report Mn3+-rich manganese oxide (MnOx)-coated chromium-doped zinc gallogermanate (ZGGO) nanoparticles (Mn-ZGGOs). Enhanced XEPL and magnetic resonance (MR) imaging were investigated by the decomposition of MnOx shell in the environment of tumors. We also evaluated the tumor cell-killing mechanism by detection of reactive oxygen (ROS), lipid peroxidation and mitochondrial membrane potential changes in vitro. Furthermore, the in vivo biodistribution, imaging and therapy were studied by U87MG tumor-bearing mice.
Results: In the tumor region, the MnOx shell is quickly decomposed to produce Mn3+ and oxygen (O2) to directly generate singlet oxygen (1O2). The resulting Mn2+ transforms endogenous H2O2 into highly toxic hydroxyl radical (·OH) via a Fenton-like reaction. The Mn2+ ions and ZGGOs also exhibit excellent T1-weighted magnetic resonance (MR) imaging and ultrasensitive XEPL imaging in tumors.
Conclusion: Both the responsive dual-mode imaging and simultaneous self-supplied O2 for the production of 1O2 and oxygen-independent ·OH in tumors allow for more accurate diagnosis of deep tumors and more efficient inhibition of tumor growth without external activation energy.
Keywords: Mn3+-rich oxide, X-ray excited persistent luminescence, tumor environment, chemodynamic therapy, responsive imaging