Journal
ACS NANO
Volume 12, Issue 2, Pages 1156-1169Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.7b06734
Keywords
superparamagnetic iron oxide nanoparticles (SPIONs); ferucarbotran; reticuloendothelial system (RES); dextran; fucoidan; single-photon emission computed tomography (SPECT); positron emission tomography (PET)
Categories
Funding
- EU [278580]
- King's College London and UCL Comprehensive Cancer Imaging Centre - Cancer Research UK (CRUK)
- EPSRC in association with the MRC and DoH (England)
- British Council
- UK Department for Business, Energy and Industrial Strategy under the Institutional Links programme [277386067]
- King's Health Partners (KHP) Research and Development Challenge Fund award [R160402]
- Centre of Excellence in Medical Engineering - Wellcome Trust
- EPSRC [WT 088641/Z/09/Z]
- Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's & St Thomas' NHS Foundation Trust and King's College London
- Celia Abrahams
- Mothers and Daughters Committee
- National Brain Appeal
- CRUK
- Department of Health (ECMC, Experimental Cancer Medicine Network Centre)
- NIHR University College London Hospitals Biomedical Research Centre
- CRUK Accelerator Grant [Cl 15121 A 20256]
- EPSRC [EP/L006472/1] Funding Source: UKRI
- MRC [MC_PC_14105] Funding Source: UKRI
- Cancer Research UK [16463] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/L006472/1] Funding Source: researchfish
- Medical Research Council [MC_PC_14105] Funding Source: researchfish
- The British Council [277386067] Funding Source: researchfish
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The magnetic properties and safety of dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) have facilitated their clinical use as MRI contrast agents and stimulated research on applications for SPIONs in particle imaging and magnetic hyperthermia. The wider clinical potential of SPIONs, however, has been limited by their rapid removal from circulation via the reticuloendothelial system (RES). We explored the possibility of extending SPION circulatory time using fucoidan, a seaweed-derived food supplement, to inhibit RES uptake. The effects of fucoidan on SPION biodistribution were evaluated using ferucarbotran, which in its pharmaceutical formulation (Resovist) targets the RES. Ferucarbotran was radiolabeled at the iron oxide core with technetium-99m (Tc-99m; t(1/2) = 6 h) or zirconium-89 (Zr-89; t(1/2) = 3.3 days). Results obtained with Tc-99m-ferucarbotran demonstrated that administration of fucoidan led to a 4-fold increase in the circulatory half-life (t(1/2) slow) from 37.4 to 150 min (n = 4; P < 0.0001). To investigate whether a longer circulatory half-life could lead to concomitant increased tumor uptake, the effects of fucoidan were tested with Zr-89-ferucarbotran in mice bearing syngeneic subcutaneous (GL261) tumors. In this model, the longer circulatory half-life achieved with fucoidan was associated with a doubling in tumor SPION uptake (n = 5; P < 0.001). Fucoidan was also effective in significantly increasing the circulatory half-life of perimag-COOH, a commercially available SPION with a larger hydrodynamic size (130 nm) than ferucarbotran (65 nm). These findings indicate successful diversion of SPIONs away from the hepatic RES and show realistic potential for future clinical applications.
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