Mn(3+)-rich oxide/persistent luminescence nanoparticles achieve light-free generation of singlet oxygen and hydroxyl radicals for responsive imaging and tumor treatment

富含Mn(3+)的氧化物/长余辉纳米粒子可在无光照条件下产生单线态氧和羟基自由基,用于响应式成像和肿瘤治疗。

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Abstract

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 Mn(3+)-rich manganese oxide (MnO(x))-coated chromium-doped zinc gallogermanate (ZGGO) nanoparticles (Mn-ZGGOs). Enhanced XEPL and magnetic resonance (MR) imaging were investigated by the decomposition of MnO(x) 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 MnO(x) shell is quickly decomposed to produce Mn(3+) and oxygen (O(2)) to directly generate singlet oxygen ((1)O(2)). The resulting Mn(2+) transforms endogenous H(2)O(2) into highly toxic hydroxyl radical (·OH) via a Fenton-like reaction. The Mn(2+) ions and ZGGOs also exhibit excellent T(1)-weighted magnetic resonance (MR) imaging and ultrasensitive XEPL imaging in tumors. Conclusion: Both the responsive dual-mode imaging and simultaneous self-supplied O(2) for the production of (1)O(2) 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.

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