A pH-Activable Chemo–Photodynamic Therapy Based on Cube-Wrapped-Cube α-NaYbF<sub>4</sub>:Tm@CaF<sub>2</sub>/Nd@ZnO Nanoparticles Mediated by 808 nm Light
Qi Cai, Dan Yang, Lei Zhong, Piaoping Yang
Abstract
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.