The specific diagnosis and treatment of gliomas is a primary challenge in clinic due to their high invasiveness and blood-brain barrier (BBB) obstruction. It is highly desirable to find a multifunctional agent with good BBB penetration for precise theranostics. Herein, we design and construct a core-shell structured nanotheranostic agent (YVO4:Nd3+-HMME@MnO2-LF, marked as YHM) with YVO4:Nd3+ particles as the core and MnO2 nanosheets as the shell. 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. The YVO4:Nd3+ (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. MnO2 shell can not only provide O2 in the tumor microenvironments (TME) to significantly improve the healing efficacy of SDT, but also release Mn2+ ions to achieve T1-weight MRI in situ. Non-invasive SDT can effectively restrain tumor growth. 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.

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