UPAR targeted phototheranostic metal-organic framework nanoprobes for MR/NIR-II imaging-guided therapy and surgical resection of glioblastoma

Abstract

Glioblastoma (GBM) is the most malignant brain tumor. Owing to its highly infiltrative nature and restrictive blood-brain tumor barrier (BBTB), the current treatment strategies, including surgery and the following chemoradiotherapy, offer very low efficacy. Therefore, it is highly desirable to develop novel multifunctional theranostic agents for visualized diagnosis and treatment of GBM. In this work, a phototheranostic nanoprobe (CH4T@MOF-PEG-AE), constructed of Fe-based metal-organic framework (MOF) nanoparticles loaded with a small-molecule near-infrared II (NIR-II) fluorophore (CH4T), is rationally designed and modified with tumor-targeting AE105 peptide for efficiently targeting the over-expressed urokinase Plasminogen Activator Receptor (uPAR) on GBM. The nanoplatform combines advantages of high penetration depth of magnetic resonance (MR) imaging with high detection sensitivity and spatiotemporal resolution of NIR-II fluorescence imaging, enabling it to diagnose and delineate GBM accurately. Besides, in vivo studies reveal that CH4T@MOF-PEG-AE can realize MR/NIR-II imaging-guided photothermal therapy (PTT), achieving successful ablation of U87MG tumors. More importantly, the nanoprobes can efficiently transport across the BBTB facilitated by active tumor-targeting and enrich in the orthotopic GBM tumors, being capable of guiding the surgical resection of GBM via real-time intraoperative NIR-II imaging. Our work provides new insights into developing theranostic nanoplatforms for efficient diagnosis and treatment of GBM.