Mn³⁺-rich oxide/persistent luminescence nanoparticles achieve light-free generation of singlet oxygen and hydroxyl radicals for responsive imaging and tumor treatment

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. <b>Methods:</b> Herein, we report Mn³⁺-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 <i>in vitro</i>. Furthermore, the <i>in vivo</i> biodistribution, imaging and therapy were studied by U87MG tumor-bearing mice. <b>Results:</b> In the tumor region, the MnO_x 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. <b>Conclusion:</b> 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.