H₂O₂-Responsive Gold Nanoclusters @ Mesoporous Silica @ Manganese Dioxide Nanozyme for “Off/On” Modulation and Enhancement of Magnetic Resonance Imaging and Photodynamic Therapy

In order to achieve safe and high-efficient photodynamic therapy (PDT), it was a powerful strategy of constructing O2-generated nanozyme with intelligent “off/on” modulation and enhancement. Herein, a kind of H2O2-responsive nanozyme was developed for off/on modulation and enhancement of magnetic resonance (MR) imaging and PDT, in which great amounts of gold nanoclusters (AuNCs) were loaded into mesoporous silica to form nanoassembly, and manganese dioxide (MnO2) nanosheets were wrapped as switching shield shell (AuNCs@mSiO2@MnO2). In a neutral physiological environment, stable MnO2 shells eliminated singlet oxygen (1O2) generation to switch off PDT and MR imaging. However, in an acidic tumor microenvironment, the MnO2 shell reacted with H2O2, in which MnO2 degradation switched on MR imaging and PDT, and the generated O2 further enhanced PDT. H2O2-responsive MnO2 degradation brought about excellent MR imaging with a longitudinal relaxation rate of 25.31 mM–1 s–1, and simultaneously sufficient O2 generation guaranteed a 74% high 1O2 yield. Under the irradiation of a 635 nm laser, the viability of MDA-MB-435 cells was reduced to 4%, and the tumors completely disappeared, demonstrating strong PDT performance. Therefore, H2O2-responsive AuNCs@mSiO2@MnO2 nanozyme showed excellent off/on modulation and enhancement of MR imaging and PDT and was a promising intelligent nanoprobe for safe and high-efficiency theranostics.