Ternary Heteronanocrystals with Dual-Heterojunction for Boosting Near-Infrared-Triggered Photo-Chemodynamic Therapy

Strongly coupled interfaces in the epitaxial growth heteronanocrystals (HNCs) provide advanced functionalities regarding interface connection, electron transfer, and carrier separation. However, the majority of current nanocomposites primarily focus on a single heterojunction involving only two subunits, which hinders the achievement of optimized synergy energy transfer among more than two components. Herein, ternary NaGdF₄:Yb,Tm-TiO₂:F-Fe₃O₄ HNCs with dual-heterojunction were synthesized based on the crystal plane epitaxial growth strategy for boosting near-infrared (NIR)-triggered photo-chemodynamic therapy (PCDT). Fluorine is doped into TiO₂ (TiO₂:F), which not only enhances the exposure of the (001) facet of TiO₂ for Fe₃O₄ subunit growth but also promotes the growth of the NaGdF₄:Yb,Tm upconversion nanocrystal (UCNC) subunit, enabling an epitaxial combination of all three components. Upon NIR irradiation, the UCNC subunit transfers the light energy of the absorbed NIR light to the TiO₂:F subunit, thereby facilitating the generation of electron-hole pairs within TiO₂:F. Due to different work functions between TiO₂:F and Fe₃O₄ in the ternary HNCs, electrons tend to transfer from TiO₂:F into Fe₃O₄, resulting in a reduction of inactive Fe³⁺ into active Fe²⁺ and further enhancing the Fenton-catalysis performance. Simultaneously, the efficient separation of electrons and holes improves the photocatalytic oxidation property induced by TiO₂:F. Based on ternary UCNC-TiO₂:F-Fe₃O₄ HNCs boosting Fenton catalysis and photocatalysis at the single particle level, as a proof of concept, we propose a NIR light-triggered PCDT (NIR-PCDT) synergistically enhanced tumor treatment strategy. In vitro and in vivo experiments demonstrate that this NIR-PCDT agent exhibits a pronounced ability to generate reactive oxygen species, effectively inducing apoptosis in tumor cells.