Ho³⁺ doped NaGdF₄ nanoparticles as MRI/optical probes for brain glioma imaging

Lanthanide-ion doped NaGdF₄ nanoparticles (NPs) have been exploited as a new generation of MRI/optical probes. However, it remains difficult for these NPs to image tiny brain gliomas due to low specificity and limited accumulation. To circumvent this obstacle, chlorotoxin (CTX) was conjugated onto Ho³⁺ doped NaGdF₄ (CTX-NaGdF₄:Ho³⁺) to render a glioma-specific targeted MRI/optical probe. Both confocal laser scanning microscopy and flow cytometry demonstrated the targeting ability of CTX-NaGdF₄:Ho³⁺ NPs towards glioma cells in vitro. Furthermore, in vivo MRI and fluorescence imaging of the tiny brain gliomas in mice confirmed that the CTX-NaGdF₄:Ho³⁺ NPs could lead to a significant contrast enhancement effect and a clearer boundary between glioma and normal tissue. In addition, the CTX-NaGdF₄:Ho³⁺ NPs exhibited a low cytotoxicity and no detectable tissue damages. Therefore, the CTX-NaGdF₄:Ho³⁺ NPs could potentially serve as an MRI/optical probe for the detection of tiny brain gliomas.