Modulation of Ultrasmall Bismuth-Doped Ferrite Nanocomposites for Trimodal Imaging-Guided NIR-II Phototherapy by Dopant Content Optimization

Doping magnetic nanoparticles (MNPs) with transition metal ions can improve their magnetic characteristics and confer a theranostic performance. However, optimizing the dopant content to balance the comprehensive theranostic capacities remains a challenge. In this study, we synthesized a series of ultrasmall ferrite nanocomposites with various Bi dopant contents (Bi x -γFe 2 O 3, x = 0.14, 0.27, and 0.41) and systematically evaluated their capabilities as MRI/CT/PAI trimodal imaging and NIR-II photothermal agents. The X-ray attenuation coefficient and NIR absorption capacity of Bi x -γFe 2 O 3 increased with increasing Bi dopant levels, indicating enhanced CT and PA imaging performance. Conversely, the saturation magnetization and T 2 contrast ability diminished progressively with increasing Bi content. Notably, Bi 0.27 -γFe 2 O 3 had the lowest r 2 / r 1 value, while maintaining an acceptable r 1 relaxivity (1.23 mM –1 s –1 ), thus making it an optimal agent for MRI ( T 1 )/CT/PAI contrast and NIR-II photothermal therapy. In vitro and in vivo experiments verified that the paradigm of Bi 0.27 -γFe 2 O 3 can realize simultaneous trimodal imaging-guided tumor ablation under NIR-II laser irradiation. Our work demonstrates a facile route for the modulation of multifunctional nanomaterials with multifarious roles in cancer theranostics and provides useful guidance toward developing heavy metal ion-doped high-performance magnetic nanocomposites for biomedical applications.