A pH-Activable Chemo–Photodynamic Therapy Based on Cube-Wrapped-Cube α-NaYbF₄:Tm@CaF₂/Nd@ZnO Nanoparticles Mediated by 808 nm Light

Photodynamic therapy (PDT) has greatly been hindered by its extreme dependence on oxygen, undesired local photodamage, and a shallow tissue penetration depth. Chemotherapy always encounters obstacle of the uncontrolled premature release of drugs. Here, we developed a novel α-NaYbF4:Tm@CaF2:Nd@ZnO–PAA–DOX (named as UZNPs–PAA–DOX) nanoplatform for combined PDT and chemotherapy mediated by 808 nm near-infrared (NIR) light. In this nanoplatform, the core–shell–shell structured α-NaYbF4:Tm@CaF2:Nd@ZnO nanoparticles (abbreviated as UZNPs) were first constructed in an epitaxial growth manner, which assembled α-NaYbF4:Tm core with a payload of endogenous CaF2 layer and further epitaxially cultivated efficient photosensitizer ZnO. It is noted that the cubic ZnO layer can directly coat on α-NaYbF4:Tm@CaF2:Nd attributing to crystal lattice matching, which has never been reported before. The reasonable Yb3+/Tm3+/Nd3+ tri-doping can regulate NIR wavelength excitation at 808 nm with low photodamage and high penetration depth. The ultraviolet emission from the NIR-radiated nanoparticles facilitates the emergence of hole–electron pairs in a ZnO photosensitizer, leading to the evolution of cytotoxic hydroxyl radicals which severely depletes the oxygen dependence. After developing a polyacrylic acid (PAA) coating with accommodation of chemo-drug doxorubicin (DOX), a large amount of DOX can be effectively released at tumor sites in response to acidity-aroused PAA disintegration. Our work may propose a new concept to design a NIR light-medicated oncotherapy nanoplatform applicable for other nanoplatforms.