A blood-brain barrier-penetrating nanoreactor for tumor microenvironment modulation, precise MR imaging and synergistic therapy of glioma

Nanomaterials-based theranostic strategy have emerged as innovative techniques for gliomas treatment. However, the existence of blood-brain barrier (BBB) hinders efficient drug delivery to glioma, and the hypoxic condition of tumor microenvironment (TME) significantly reduces therapeutic efficacy. Thus, in this study, we developed a novel reactive oxygen species (ROS)-generating nanoplatform responsive to the TME. This platform utilized mesoporous PtNi nanoparticles (NPs) as carriers, loaded with chelated gadolinium porphyrin (Gd-HMME), to enable combined sonodynamic and chemodynamic therapy under magnetic resonance imaging (MRI) guidance. Employing a transferrin (Tf)-mediated trans-BBB strategy, Tf-PtNi@Gd-HMME-PEG (TPGP) precisely targeted and penetrated glioma tissues, facilitating T1-weighted enhanced imaging of tumor regions. The MRI enhancement signal achieved was 1.64-fold of the control group. Concurrently, the intrinsic acoustic sensitivity and enzyme-like catalytic activity of TPGP produce substantial ROS under ultrasound stimulation. These ROS interact with hydrogen peroxide in the TME to generate toxic free radicals, collectively acting on tumor cells to deliver a dual assault via sonodynamic and chemodynamic mechanisms to effectively inhibit tumor growth and ameliorate the tumor microenvironment. This study underscores the potential of TPGP as a multifunctional nanoplatform for targeted glioma therapy, combining diagnostic imaging with synergistic therapy to overcome the BBB and hypoxic TME. • A novel catalytic PtNi (TPGP) nanozyme responsive to the tumor microenvironment was developed. • TPGP facilitated efficient BBB crossing by leveraging surface-modified transferrin (Tf). • The TPGP nanozyme exhibited enhanced MR contrast and superior MR imaging effect in vivo. • TPGP nanozyme induced robust ROS production from synergistic CDT/SDT for excellent glioma inhibition outcomes.