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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.