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.

In spite of the tumor microenvironments responsive cancer therapy based on Fenton reaction (i.e., chemodynamic therapy, CDT) has been attracted more attentions in recent years, the limited Fenton reaction efficiency is the important obstacle to further application in clinic. Herein, we synthesized novel FeO/MoS2 nanocomposites modified by bovine serum albumin (FeO/MoS2-BSA) with boosted Fenton reaction efficiency by the synergistic effect of co-catalyze and photothermal effect of MoS2 nanosheets triggered by the second near-infrared (NIR II) light. In the tumor microenvironments, the MoS2 nanosheets not only can accelerate the conversion of Fe3+ ions to Fe2+ ions by Mo4+ ions on their surface to improve Fenton reaction efficiency, but also endow FeO/MoS2-BSA with good photothermal performances for photothermal-enhanced CDT and photothermal therapy (PTT). Consequently, benefiting from the synergetic-enhanced CDT/PTT, the tumors are eradicated completely in vivo. This work provides innovative synergistic strategy for constructing nanocomposites for highly efficient CDT.