MSOT/CT/MR imaging Guided and hypoxia Maneuvered Oxygen self-sufficiency radiotherapy based on One-pot MnO2-mSiO2 @ Au nanoparticle

摘要： Radiotherapy (RT) is one of the most widely applied treatments for cancer therapy in the clinic. Herein, we constructed an innovative multifunctional nanotheranostic MnO2-mSiO2@Au-HA nanoparticles (MAHNPs) based on one-pot MnO2-mSiO2 nanohybrids (MNHs) and gold nanoparticles (AuNPs) for multispectral optoacoustic tomography (MSOT)/ computed tomography (CT) and magnetic resonance (MR) imaging guided hypoxia-maneuvered radiotherapy. The MNHs were prepared by a facile one-pot approach which avoided the leakage of MnO2 nanoparticles as well as increased the efficiency on preparation. The Mn2+ ions could trigger the breakdown of endogenous H2O2 to generate O2 to convert the hypoxic tumor micro-environment (TME), thus enhancing radiotherapy by self-sufficiency oxygen. In addition, hyaluronic acid (HA) was employed to modify the surface of MnO2-mSiO2@Au nanoparticles to improve biocompatibility and cellular uptake. The well-designed nanoparticles could perform remarkable photothermal therapy (PTT) and hypoxia-maneuvered radiotherapy (RT) simultaneously as well as MSOT/CT/MR imaging. In vivo studies showed that MAHNPs achieved almost entirely suppression of tumor growth without observable recurrence, which raised new possibilities for clinical nanotheranostics with multimodal diagnostic and therapeutic coalescent design.