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

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1660-1670页

作者： 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 Department of Chemistry Department of Materials Science and Engineeringand Department of Chemical EngineeringTexas A&M UniversityCollege StationTX 77842USA Laboratory of Macromolecular and Organic Chemistry and Institute for Complex Molecular Systems Eindhoven University of TechnologyEindhovenMB 5600The Netherlands Mallinckrodt Institute of Radiology Washington University School of MedicineSaint LouisMO 63110USA Bayer AG Creve CoeurMO 63167USA

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 *** 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 *** formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca.10 nm in water was confirmed by dynamic and static light scattering *** a breast cancer mouse model,in vivo biodistribution studies revealed that the64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging ***/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.

关键词： Amphiphilic statistical iodocopolymer CT X-ray contrast media Ultrasmall nanoassembly PET/CT Longitudinal tumor monitoring

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