Ultrasmall, elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers

Lu Su; Kellie S. Dalby; Hannah Luehmann; Sussana A. Elkassih; Sangho Cho; Xun He; Lisa Detering; Yen-Nan Lin; Nari Kang; Dennis A. Moore; Richard Laforest; Guorong Sun; Yongjian Liu; Karen L. Wooley

Acta Pharmaceutica Sinica B (Apr 2023)

Ultrasmall, elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers

Lu Su,
Kellie S. Dalby,
Hannah Luehmann,
Sussana A. Elkassih,
Sangho Cho,
Xun He,
Lisa Detering,
Yen-Nan Lin,
Nari Kang,
Dennis A. Moore,
Richard Laforest,
Guorong Sun,
Yongjian Liu,
Karen L. Wooley

Affiliations

Lu Su: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA; Laboratory of Macromolecular and Organic Chemistry and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, MB 5600, The Netherlands
Kellie S. Dalby: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA
Hannah Luehmann: Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Sussana A. Elkassih: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA
Sangho Cho: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA
Xun He: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA
Lisa Detering: Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Yen-Nan Lin: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA
Nari Kang: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA
Dennis A. Moore: Bayer AG, Creve Coeur, MO 63167, USA
Richard Laforest: Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
Guorong Sun: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA; Corresponding author.
Yongjian Liu: Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Corresponding author.
Karen L. Wooley: Department of Chemistry, Department of Materials Science and Engineering, and Department of Chemical Engineering, Texas A&M University, College Station, TX 77842, USA; Corresponding author.

Journal volume & issue: Vol. 13, no. 4
pp. 1660 – 1670

Abstract

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To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10 nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, in vivo biodistribution studies revealed that the 64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.

Published in Acta Pharmaceutica Sinica B

ISSN: 2211-3835 (Print); 2211-3843 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/acta-pharmaceutica-sinica-b

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