Although advanced molecular imaging techniques can be used for glioma diagnosis, their low spatial resolution, harmful ionization, and complicated workflow limit their application in real-time intraoperative imaging 4, 5, 6. Glioma is an intracranial malignant tumor that still poses a major clinical challenge due to its highly invasive nature, low cure rate, and high mortality rate 1, 2, 3. This work not only demonstrates that multifunctional YHM is promising for diagnosis and treatment of orthotopic glioma, but also provides insights into exploring the theranostic agents based on rare earth-doped yttrium vanadate nanoparticles. Non-invasive SDT can effectively restrain tumor growth. MnO 2 shell can not only provide O 2 in the tumor microenvironments (TME) to significantly improve the healing efficacy of SDT, but also release Mn 2+ ions to achieve T 1-weight MRI in situ. The YVO 4:Nd 3+ (25%) core exhibited good NIR-II fluorescence properties, enabling YHM to act as promising probes for NIR-II fluorescence imaging of vessels and orthotopic gliomas. Sonosensitizer hematoporphyrinmonomethyl ether (HMME) and lactoferrin (LF) were further loaded and modified on the surface, giving it a good ability to cross the BBB, near-infrared fluorescence imaging in the second window (NIR-II)/magnetic resonance imaging (MRI) bimodality, and highly efficient sonodynamic therapy (SDT) of orthotopic gliomas. Herein, we design and construct a core-shell structured nanotheranostic agent (YVO 4:Nd 2-LF, marked as YHM) with YVO 4:Nd 3+ particles as the core and MnO 2 nanosheets as the shell. It is highly desirable to find a multifunctional agent with good BBB penetration for precise theranostics. The specific diagnosis and treatment of gliomas is a primary challenge in clinic due to their high invasiveness and blood-brain barrier (BBB) obstruction.
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