Versatile nanocomposite augments high-intensity focused ultrasound for high-efficacy sonodynamic therapy of glioma

High-intensity focused ultrasound (HIFU), with inherent advantages of improved ultrasonic depth and low off-target damage, holds the promising capability for glioma treatment, but the relatively long therapeutic time and potential physical complications may hamper its clinical application. Herein, a bovine serum albumin (BSA)-based nanoplatform with in situ growth of MnO2 was synthesized, and Protoporphyrin IX (PpIX) was further anchored to obtain a versatile PpIX@MnO2@BSA nanoplatform (denoted as BMP). By employing HIFU as the exogenous irradiation source, a high-efficacy sonodynamic therapy (SDT) is developed, in which the excited BMP enables the production of tumoricidal reactive oxygen species (ROS). The inherent tumor microenvironment (TME)-responsive property of MnO2 endows BMP with specific T1-weighted magnetic resonance imaging (MRI) by releasing Mn2+, and the simultaneously generated O2 facilitates hypoxia alleviation as well as 1O2 generation. Compared with HIFU therapy alone, suppression of glioma growth and improved survival benefits are achieved through the designed TME-responsive nanocomposite under HIFU exposure. The high-efficacy SDT strategy combining BMP and HIFU demonstrated favorable TME-responsive T1-weighted MRI, hypoxic environment alleviation, and anti-tumor capability, providing a perspective paradigm for MRI-guided glioma treatment.