Glutathione-Mediated Clearable Nanoparticles Based on Ultrasmall Gd2O3 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 (Gd2O3) nanoparticles, which possess the advantage of high longitudinal relaxation rate, were coated with bovine serum albumin (BSA). After the Gd2O3/BSA nanoparticles were linked with two-dimensional photothermal MoS2 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 Gd2O3/BSA@MoS2-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 Gd2O3/BSA@MoS2-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.