Versatile metal-phenolic network nanoparticles for multitargeted combination therapy and magnetic resonance tracing in glioblastoma.

Abstract Glioblastoma multiforme (GBM) is a common malignancy of the central nervous system, but conventional treatments yield unsatisfactory results. Although innovative therapeutic approaches have been developed, they prolong survival by only approximately 5 months. The heterogeneity of GBM renders growth inhibition with a single drug difficult, and exploring combination approaches with multiple targets for the comprehensive treatment of GBM is expected to overcome this limitation. In this study, we designed a biocompatible cRGD/Pt + DOX@GFNPs (RPDGs) nanoformulation to disrupt redox homeostasis in GBM cells and promote the simultaneous occurrence of efficient apoptosis and ferroptosis. Taking advantage of the highly stable Fenton reaction catalytic activity of gallic acid (GA)/Fe2+ nanoparticles in physiological environments, the ability of Pt (IV) to deplete glutathione (GSH) and increase reactive oxygen species (ROS) levels, and the efficient photothermal conversion efficiency of GA/Fe2+ nanoparticles, our synthesized multifunctional and multitargeted RPDGs significantly increased intracellular ROS levels and thus induced ferroptosis. Furthermore, the RPDGs displayed superior photothermal responsiveness and magnetic resonance imaging (MRI) capabilities. These results indicate that RPDGs can not only directly inhibit the growth of tumors but also effectively improve the efficient translocation of conventional chemotherapeutic drugs across the blood-brain barrier, thereby providing a new approach for the comprehensive treatment of GBM.