Synergistic upconversion photodynamic and photothermal therapy under cold near-infrared excitation

Lanthanide-doped upconversion nanoparticles (UCNPs) have been extensively investigated due to their unique capabilities of upconverting near-infrared light (NIR) to visible/ultraviolet emission. However, use of conventional Yb-based UCNPs under 980 nm excitation for biomedical applications is limited due to the overheating caused by the strong light absorption by water at this wavelength. Although this could be improved by using Nd³⁺-Yb³⁺ codoped UCNPs and changing the excitation wavelength to 808 nm, the amount of Nd³⁺ doping is usually below 20 mol% due to the lattice strain in highly Nd-doped core–shell structures. In this study, we report Nd³⁺-sensitized NaYF₄:Yb,Er@NaLuF₄:Nd@NaLuF₄ UCNPs, in which the NaLuF₄ in the intermediate shell can accommodate more structural changes caused by the Nd³⁺ doping, and allow for high concentration of Nd³⁺ doping (up to 50 mol%). Due to such high Nd³⁺ doping in the nanostructure, the red and green upconversion emissions of as-synthesized UCNPs are significantly increased upon 808 nm excitation, which are used to activate two photosensitizer drugs, MC540 (merocyanine 540) and FePc (iron phthalocyanine), for the dual photodynamic and photothermal therapy. The results show that the generation of reactive oxygen species (ROS) upon 808 nm light excitation is substantially boosted due to the synergistic therapeutic effect, which significantly prohibits the growth of cancer cells. It is believed that the nanoplatform specially developed in this study can solve the overheating issue associated with the 980 nm light excitation and the combined photodynamic and photothermal therapy can significantly improve the cancer therapy efficacy. © 2021 Elsevier Inc.