To develop gadolinium alginate-based hydrogel as embolic agent and explore its applications in theranostics. Gadolinium alginate hydrogel consists of biocompatible alginate polymers cross-linked by gadolinium ions which confer magnetic resonance imaging (MRI) and X-ray contrast enhancement. An embolic agent which can deliver multiple chemotherapeutic agents and is inherently contrast-enhancing without addition of further material is highly desirable. Gadolinium-alginate hydrogel beads were synthesized by the addition of 1-3% sodium alginate (Sigma-Aldrich, St. Louis, MO) into a flask of 10% (w/w) gadolinium acetate solution (Sigma-Aldrich, St. Louis, MO) under magnetic stirring. Bead morphology was examined using scanning electron microscopy (SEM) of the dried beads. Radiopacity of the spheres was obtained using Explore Locus RS micro-CT (GE Medical Systems, London Ontario). In vitro viability assay and fluorescence microscopy imaging were conducted by incubating glioblastoma cell lines, U87MG, U251, and a patient-derived line, with gadolinium-alginate spheres for 24 hours. Synthesized gadolinium alginate beads have an average diameter of ∼2000 nm and a density of 0.7-1.3 g/cm 3 . SEM micrographs of beads showed wrinkled surface morphology which could be well suited for binding of drugs. Increased radiopacity was observed with Hounsfield units (HU) values of 450-900. The synthesized beads reduced the viability of three separate glioblastoma cell lines across multiple doses. Specifically, for U87MG cells, it reduced viability ∼30% compared to a viability of ∼90% against conventionally used calcium alginate beads. Our results showed that we have successfully synthesized and characterized gadolinium alginate which has contrast-enhancing properties. It could be loaded with therapeutic drugs for controlled release, applied as embolic material, and serve as a versatile theranostic material. Added advantage with these beads are the cost-effectiveness, radiopacity, straightforward synthesis, and ease of loading with hydrophobic drugs that are not generally suitable for typical IV administration. Currently, we are working to develop gadolinium alginate nanobeads with improved features for in vivo applications.
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Owens et al. (2024) studied this question.
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