HO-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 O-generated nanozyme with intelligent "off/on" modulation and enhancement. Herein, a kind of HO-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 (MnO) nanosheets were wrapped as switching shield shell (AuNCs@mSiO@MnO). In a neutral physiological environment, stable MnO shells eliminated singlet oxygen (O) generation to switch off PDT and MR imaging. However, in an acidic tumor microenvironment, the MnO shell reacted with HO, in which MnO degradation switched on MR imaging and PDT, and the generated O further enhanced PDT. HO-responsive MnO degradation brought about excellent MR imaging with a longitudinal relaxation rate of 25.31 mM s, and simultaneously sufficient O generation guaranteed a 74% high O 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, HO-responsive AuNCs@mSiO@MnO 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.