Gram-scale synthesis of nanotherapeutic agents for CT/T1-weighted MRI bimodal imaging guided photothermal therapy

Theranostic nanomedicine, which uses both imaging and therapeutic components for simultaneous disease diagnosis and treatment, is expected to improve patient treatment safety and outcomes by offering a more personalized approach to medicine. However, the poor reproducibilities of nanomedicines synthesized for optimized bioavailability and their potential toxicity are impeding clinical development. Moreover, milligram-scale synthetic methods are often inconsistent when transferred to mass production. To address these challenges, a facile, room temperature, aqueous phase synthesis of nanotheranostic agents using clinically validated mesoporous silica and naturally derived polydopamine has been developed. Since the synthetic procedure is simple and robust, and requires only simple mixing under ambient conditions, excellent batch-to-batch consistency has been achieved. As a result, this process can be easily scaled-up to produce gram-scale batches with physicochemical parameters similar to those of materials synthesized in smaller batches. The resulting nanotheranostic agents exhibit efficient X-ray tomography and T1-weighted magnetic resonance image contrast enhancing abilities due to their chemically ligated, benign Bi3+ and Fe3+ ions. Furthermore, the inclusion of a polydopamine shell makes the nanoparticle surface easy to functionalize and renders these materials highly efficient as photothermal agents. These nanotheranostic agents are suitable for mass production and for potential applications in multimodal imaging-guided therapy in clinical settings.