ZnAl₂O₄:Er³⁺ Upconversion Nanophosphor for SPECT Imaging and Luminescence Modulation via Defect Engineering

This work reports an "all-in-one" theranostic upconversion luminescence (UCL) system having potential for both diagnostic and therapeutic applications. Despite considerable efforts in designing upconversion nanoparticles (UCNPs) for multimodal imaging and tumor therapy, there are few reports investigating dual modality SPECT/optical imaging for theranostics. Especially, research focusing on in vivo biodistribution studies of intrinsically radiolabeled UCNPs after intravenous injection is of utmost importance for the potential clinical translation of such formulations. Here, we utilized the gamma emission from ¹⁶⁹Er and ¹⁷¹Er radionuclides for the demonstration of radiolabeled ZnAl₂O₄:^171/169Er³⁺ as a potent agent for dual-modality SPECT/optical imaging. No uptake of radio nanoformulation was detected in the skeleton after 4 h of administration, which evidenced the robust integrity of ZnAl₂O₄:^169/171Er³⁺. Combining the therapeutics using the emission of β^- particulates from ¹⁶⁹Er and ¹⁷¹Er will be promising for the radio-theranostic application of the synthesized ZnAl₂O₄:^169/171Er³⁺ nanoformulation. Cell toxicity studies of ZnAl₂O₄:1%Er³⁺ nanoparticles were examined by an MTT assay in B16F10 mouse melanoma cell lines, which demonstrated good biocompatibility. In addition, we explored the mechanism of UCL modulation via defect engineering by Bi³⁺ codoping in the ZnAl₂O₄:Er³⁺ upconversion nanophosphor. The UCL color tuning was successfully achieved from the red to the green region as a function of Bi³⁺ codoping concentrations. Further, we tried to establish a correlation of UCL tuning with the intrinsic oxygen and cation vacancy defects as a function of Bi³⁺ codoping concentrations with the help of electron paramagnetic resonance (EPR) and positron annihilation lifetime spectroscopy (PALS) studies. This study contributes to building a bridge between nature of defects and UC luminescence that is crucial for the design of advanced UCNPs for theranostics.