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One restriction to the development and application of transcatheter arterial chemoembolization (TACE) therapy is the lack of an inherently radiopaque embolic whose location and distribution can be precisely visualized in real time and be used for non-invasive examination after surgery. Methods: A one-step electrospray method was developed to fabricate calcium alginate microspheres loaded with tantalum nanoparticles (Ta@CaAlg). The parameters of electrospraying were assessed. The in vivo X-ray imaging capability and embolic effect of Ta@CaAlg microspheres were evaluated in the renal arteries of normal rabbits by digital radiography and computed tomography. Doxorubicin hydrochloride (Dox) was chosen as a model drug, and the drug loading capacity and release behavior of these microspheres was valuated in vitro.  Results: Spherical Ta@CaAlg microspheres with monodisperse sizes ranging from 150 to 1200 μm were fabricated by electrospraying. The results of an in vivo study showed that Ta@CaAlg microspheres possessed the qualities of both embolic agents and contrast media. They could not only feed back the real-time location and distribution of the embolic microspheres but also maintained clear X-ray imaging of embolized sites for up to 4 weeks as assessed by digital radiography and computed tomography. Digital subtraction angiography showed that they had an excellent embolic effect. Ta@CaAlg microspheres could be loaded with Dox to form "3-in-1" embolic microspheres. The maximum Dox loading was 97.3 mg Dox per mL beads and loaded microspheres exhibited pH-dependent release profiles. Conclusion: The X-ray opacity and drug-loading capability of Ta@CaAlg microspheres offers great promise in direct, real-time, in vivo investigation for TACE and long-term non-invasive re-examination.

Radiopaque and uniform alginate microspheres loaded with tantalum nanoparticles for real-time imaging during transcatheter arterial embolization