Info
Background:
Background:
Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma, combining localized chemotherapy with embolization to block tumor blood supply. However, current embolic agents limited in their capacity to deliver multiple chemotherapeutic agents simultaneously.
Hypothesis/Objective:
Objective:
To develop and characterize a novel microsphere-based embolic platform that is both CT-visible and capable of loading two ionically distinct chemotherapeutic drugs, enabling image-guided, customizable TACE.
Methods:
Methods:
We synthesized iodinated or bismuth polymeric microspheres from clinically approved Embozene microsphere for dual-drug loading via surface and internal functionalization. Modifications, physical properties such as sphericity after functionalization, CT visibility and elemental mapping of radiopaque elements were evaluated using Kaiser test, combustion analysis, Attenuated total reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), ion chromatographic technique was used to determine iodine content, upright microscope, microCT imaging and scanning electron microscope, respectively.
Results:
Results:
Iodinated and bismuth chelated microspheres were successfully synthesized from clinically approved Embozene microspheres. The synthesized microspheres at each step were monitored by Kaiser test and the final product maintained an intact spherical morphology when examined by upright microscopy, confirming their structural stability under the applied reaction conditions. Combustion analysis, iodine test using ion chromatography and ATR-FTIR spectroscopy confirmed functionalization of the beads and conjugation of iodinated moiety. MicroCT imaging revealed strong radiographic contrast for individual microspheres, enabling clear visualization under clinically relevant settings. Elemental mapping using SEM-EDX further confirmed that the radiopaque elements—iodine and bismuth—were uniformly distributed within the respective iodinated and bismuth-chelated microspheres. In addition, the microspheres contain both carboxylic and amine functional groups within their matrix, enabling the loading of ionically distinct chemotherapeutics. This dual functionality demonstrates the capacity to co-load drugs with different ionic properties, which may lead to synergistic tumor-killing effects and facilitate the investigation of synergistic drug combinations.
Conclusion:
Conclusion:
These CT-visible, dual-drug-loadable microspheres represent a promising platform for image-guided TACE, offering improved therapeutic control through real-time imaging, enhanced bioavailability of synergistic drugs, and flexible drug delivery. This system may enable better tumor targeting, optimized treatment planning, and improved post-procedural monitoring in clinical applications.
Acknowledgements:
This research was supported [in part] by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.
Image/Figure:
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Image/Figure Caption:
Figure. Schematic representation of amine functionalization of Embozene microspheres, followed by conjugation of the free amine groups with triiodobenzoic acid using EDC-mediated coupling (A). (B) FT-IR spectra of (1) COOH-functionalized bland beads (Microsphere 1), (2) amine/amide-functionalized beads (Microsphere 2), and (3) triiodobenzoic acid–conjugated beads (Microsphere 3). Spectrum 1 shows characteristic carboxylic acid bands (broad O–H, ~1707 cm⁻¹ C=O). Spectrum 2 exhibits amide I (~1621 cm⁻¹) and amide II (~1551 cm⁻¹) bands, confirming amide formation with residual COOH (~1715 cm⁻¹). Spectrum 3 retains carboxylic acid (~3400, 1724 cm-1), amide bands (~1647 and ~1519 cm⁻¹) and displays diagnostic iodinated aromatic C–I stretches (~606 and ~504 cm⁻¹) and aromatic out-of-plane bands (~864 and ~748 cm⁻¹), confirming successful triiodobenzoic conjugation and (C) MicroCT imaging of radiopaque microspheres. (A) Axial slice of a suspension containing iodinated microspheres (Microsphere 3).
Author
Ayele Negussie
National Institutes of Health (NIH)