Imaging-guided sonodynamic therapy of glioma through iRGD-modified manganese-porphyrin loaded nanoparticles

Sonodynamic therapy (SDT) represents a promising modality for oncological treatment; however, its application in glioma management is hindered by several critical barriers, including inadequate penetration of the blood-brain barrier (BBB), the inability to monitor intracranial targeting in real time, and the lack of image guidance for treatment localization. To address these challenges, we developed an integrated theranostic nanoplatform, iRGD-LP-DM, comprising iRGD peptide-modified liposomes loaded with a manganese-chelated porphyrin sonosensitizer. The system leverages iRGD-mediated active targeting to traverse the BBB while simultaneously serving as a T1-weighted MRI contrast agent. Upon tumor accumulation, ultrasound irradiation activates the sonosensitizer, triggering localized reactive oxygen species (ROS) generation and apoptotic cell death. In vitro and in vivo evaluations confirmed the enhanced glioma-targeting and deeper tissue penetration of iRGD-LP-DM, which was effectively tracked in real time via MRI. When combined with ultrasound irradiation, iRGD-LP-DM elicited significantly stronger antitumor efficacy and prolonged survival in orthotopic glioma-bearing mice compared with all control groups. This work presents a multifunctional nanotheranostic platform that synchronizes active tumor targeting, real-time MRI guidance, and localized SDT, offering a compelling strategy for precision, image-guided treatment of glioma.