Rationally Designed Monodisperse Gd₂O₃/Bi₂S₃ Hybrid Nanodots for Efficient Cancer Theranostics

Abstract Multifunctional nanotheranostic agents are of particular importance in the field of precise nanomedicine. However, a critical challenge remains in the rational fabrication of monodisperse multicomponent nanoparticles with enhanced multifunctional characteristics for efficient cancer theranostics. Here, a rational and facile synthesis of monodisperse Gd₂O₃/Bi₂S₃ hybrid nanodots (Gd/Bi‐NDs) is demonstrated as a multifunctional nanotheranostic agent using a albumin nanoreactor for computed tomography (CT)/photoacoustics (PA)/magnetic resonance (MR) imaging and simultaneous photothermal tumor ablation. Two nanoprecipitation reactions in one albumin nanoreactor are simultaneously conducted to generate ultrasmall Gd/Bi‐NDs with both orthorhombic Bi₂S₃ and cubic Gd₂O₃ nanostructures. Their hybrid nanostructure generates distinctly enhanced longitudinal relaxivity in the spatially confined albumin nanocage as compared to monocomponent Gd₂O₃ nanodots. Moreover, such hybrid nanodots possess multiple desirable characteristics including superior photobleaching resistance, efficient cellular uptake, preferable tumor accumulation, good in vivo clearance, and negligible acute toxicity, thereby leading to complementary PA/CT/MR imaging with spatial and anatomic characteristics, as well as effective photothermal tumor ablation without regrowth. These results represent a promising approach to fabricate monodisperse multicomponent nanotheranostic agents for efficient cancer theranostics.