Engineering Tumor‐Specific Nanotheranostic Agent with MR Image‐Guided NIR‐II & ‐III Photodynamic Therapy to Combat Against Deeply Seated Orthotopic Glioblastoma

Glioblastoma multiforme (GBM) is one of the most aggressive, incurable, and difficult-to-treat malignant brain tumor with very poor survival rates. The gold standard in treating GBMs includes neurosurgical resection of the tumor, followed by the chemotherapy and radiotherapy. However, these strategies remain ineffective in treating patients with GBMs, as tumor recurrence always occur in most cases. Therefore, it remains a grand challenge to develop an effective strategy to combat orthotopic glioblastoma with simultaneous imaging capabilities to monitor the therapeutic outcomes. To tackle this challenge, this study demonstrates, for the first time, that a tumor-specific europium hexaboride (EuB6)-based nanomedicine surface-modified with RGD-K peptide to target αvβ3 integrin receptors overexpressed on the glioblastoma cells. Further, EuB6@RGD-K NPs are able to exert theranostic capabilities to effectively diagnose and combat difficult-to-treat orthotopic glioblastoma tumors using NIR-II 1064 nm and NIR-III 1550 nm photodynamic therapy (NIR PDT) effects. In the in vivo experiments, the average half-life of 55 d for mice treated with EuB6@RGD-K NPs and exposed to NIR-III 1550 nm light irradiation is far higher than that of EuB6@RGD-K NPs exposed to NIR-II 1064 nm light irradiation (25 d), PBS-treated mice (20 d) and EuB6@RGD-K NPs-treated mice (no light irradiation, 18 d). To the best of our knowledge, this work represents the first example for destructing murine brain tumors via multi-functional tumor-specific europium hexaboride-based nanotheranostic agent to mediate MR imaging-guided NIR-II/-III photodynamic therapy.