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 T-1-weighted magnetic resonance imaging (MRI) by releasing Mn-2(+), and the simultaneously generated O-2 facilitates hypoxia alleviation as well as O-1(2) 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 T-1-weighted MRI, hypoxic environment alleviation, and anti-tumor capability, providing a perspective paradigm for MRI-guided glioma treatment.