A multifunctional Fe3O4@Au-HPG-Glc theranostic platform for MRI/fluorescence-guided photothermal ablation of osteosarcoma

Abstract

Background The clinical management of osteosarcoma is challenged by its aggressive growth and deep anatomical location. Photothermal therapy offers a minimally invasive approach through localized thermal ablation, but its effectiveness is constrained by poor tissue penetration and inaccurate targeting of deep tumors without real-time guidance. Methods We synthesized flower-like Fe3O4@Au nanoparticles coated with hyperbranched polyglycerol (HPG) and conjugated with glucose (Glc) (Fe3O4@Au-HPG-Glc). In an osteosarcoma mouse model, the photothermal efficacy of the nanoprobes was evaluated by comparing two groups: the control group receiving phosphate-buffered saline plus laser irradiation (phosphate-buffered saline (PBS) + Laser) and the treatment group receiving Fe3O4@Au-HPG-Glc nanoprobes plus laser irradiation (NPs + Laser). Intratumoral temperature was monitored by infrared thermography, with longitudinal tracking of tumor volume and body weight. Major organs were examined by H&E staining. Tumor accumulation was assessed via whole-body fluorescence and T2-weighted magnetic resonance imaging (MRI); pharmacokinetics and biodistribution were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Results The NPs + Laser regimen produced rapid intratumoral heating during the 0–4 min irradiation window and significantly delayed tumor growth compared with the PBS + Laser control group, with stable body weight and no overt organ lesions on H&E staining. Whole-body fluorescence and T2-weighted MRI confirmed tumor-site accumulation of the nanoprobes. ICP-MS-based pharmacokinetic and biodistribution analyses provided quantitative exposure context, including systemic clearance, reticuloendothelial system capture, and measurable tumor uptake. Together, these data facilitated interpretation of the subsequent photothermal response. Discussion Flower-like Fe3O4@Au-HPG-Glc enables image-guided photothermal treatment in an osteosarcoma model, supported by quantitative pharmacokinetic and biodistribution measurements and an acceptable short-course safety profile. This work establishes a clear imaging-exposure-response relationship and provides a strong foundation for further optimization of magnetic-optical combination strategies in precision cancer therapy.