Magnetic continuum robot-mediated intracranial delivery of peptide nanophotosensitizers for glioblastoma photodynamic therapy

Abstract

Effective treatment of glioblastoma (GBM) remains a significant clinical challenge. Although photodynamic therapy (PDT) is a promising anticancer treatment method, its clinical application in GBM is limited by poor light penetration through the skull and insufficient drug delivery across the blood–brain barrier (BBB). Here, an innovative magnetic continuum robot (MCR)-mediated intracranial PDT strategy is proposed. The MCR enters the cranial cavity via an Ommaya device, enabling direct delivery of photodynamic nanoparticles (PNPs) to the tumor region and localized laser irradiation through an integrated optical fibre. PNPs, self-assembled from an aromatic short peptide and a porphyrin derivative, were employed owing to their favorable biocompatibility and photosensitivity. To ensure precise navigation within the brain, a closed-loop control system was developed, leveraging the MCR's active deflection capabilities under an electromagnetic driving system. In vitro studies confirmed that this PDT approach effectively induced GBM cell apoptosis, while in vivo experiments demonstrated efficient intratumoral accumulation of PNPs and significant tumor suppression. This strategy bypasses the BBB and enables site-specific light activation, thereby enhancing PDT efficacy. Overall, this robot-guided therapeutic platform represents a promising advance for precision PDT in GBM treatment.