Glutathione-Mediated Clearable Nanoparticles Based on Ultrasmall GdO for MSOT/CT/MR Imaging Guided Photothermal/Radio Combination Cancer Therapy.

Recently, multifunctional clearable inorganic theranostic nanoparticles have been attracting more and more attention. Protein-based nanoparticles can be cleared by the hepatobiliary system efficiently. In this work, ultrasmall gadolinium oxide (GdO) nanoparticles, which possess the advantage of high longitudinal relaxation rate, were coated with bovine serum albumin (BSA). After the GdO/BSA nanoparticles were linked with two-dimensional photothermal MoS nanomaterials, the nanoparticles were also modified with hyaluronic acid (HA) through the disulfide bonds for tumor-targeting effect. As indicated by in vitro and in vivo studies, these GdO/BSA@MoS-HA nanoparticles could be rapidly degraded and excreted after reacting with glutathione (GSH) by the redox response, thus avoiding long-term toxicity. In addition, the cellular uptake study and in vivo multispectral optoacoustic tomography (MSOT), X-ray computed tomography (CT), and magnetic resonance (MR) triple-modal images demonstrated that GdO/BSA@MoS-HA nanoparticles exhibited a high tumor uptake effect after intravenous injection. Consequently, such clearable theranostic nanoparticles with multiple functions, which are applicable in multimodal imaging-guided cancer therapy, might show promise for applications in nanomedical science.