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Fucoidan prolongs the circulation time of dextran-coated iron oxide nanoparticles

Fucoidan prolongs the circulation time of dextran-coated iron oxide nanoparticles
Fucoidan prolongs the circulation time of dextran-coated iron oxide nanoparticles
he 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 (99mTc; t1/2 = 6 h) or zirconium-89 (89Zr; t1/2 = 3.3 days). Results obtained with 99mTc-ferucarbotran demonstrated that administration of fucoidan led to a 4-fold increase in the circulatory half-life (t1/2 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 89Zr-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.
dextran; ferucarbotran; fucoidan; positron emission tomography (PET); reticuloendothelial system (RES); single-photon emission computed tomography (SPECT); superparamagnetic iron oxide nanoparticles (SPIONs)
1936-0851
1156-1169
Abdollah, M.R.A.
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Carter, T.J.
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Jones, C.
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Kalber, T.L.
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Rajkumar, V.
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Tolner, B.
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Gruettner, C.
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Zaw-Thin, M.
b3dcd675-c8f0-4ed8-a0c2-147a648590f4
Baguña Torres, T.
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Ellis, M.
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Robson, M.
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Pedley, R.B.
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Mulholland, P.
e1328f97-c8d8-4d48-9be2-295cc5baa454
de Rosales, R.T.M.
eafa1576-ff67-4236-9973-d2900ea9df95
Chester, K.A.
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Abdollah, M.R.A.
87db58c4-e9ca-485d-9304-c7873348684b
Carter, T.J.
b31567db-b04e-46ed-ab05-79800e4d41fc
Jones, C.
5467c8ed-b4f8-41fc-8d59-331e9543c792
Kalber, T.L.
dc3b698e-e2c3-47a0-8313-7a60215dd596
Rajkumar, V.
2fbcfec0-6974-4895-90f7-ad2e05599648
Tolner, B.
d8dfd18c-77e5-492d-93a0-d1584fa79745
Gruettner, C.
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Zaw-Thin, M.
b3dcd675-c8f0-4ed8-a0c2-147a648590f4
Baguña Torres, T.
51faa427-dd46-4da6-9340-49cc7bb379c4
Ellis, M.
afbca752-ced4-40dd-b0af-d9ecffbd5b63
Robson, M.
45dc452a-6b39-4149-b3c7-1ce564512084
Pedley, R.B.
e61e13de-a4ac-4926-ba6d-5e0a5e94f138
Mulholland, P.
e1328f97-c8d8-4d48-9be2-295cc5baa454
de Rosales, R.T.M.
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Chester, K.A.
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Abdollah, M.R.A., Carter, T.J., Jones, C., Kalber, T.L., Rajkumar, V., Tolner, B., Gruettner, C., Zaw-Thin, M., Baguña Torres, T., Ellis, M., Robson, M., Pedley, R.B., Mulholland, P., de Rosales, R.T.M. and Chester, K.A. (2018) Fucoidan prolongs the circulation time of dextran-coated iron oxide nanoparticles. ACS Nano, 12 (2), 1156-1169. (doi:10.1021/acsnano.7b06734).

Record type: Article

Abstract

he 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 (99mTc; t1/2 = 6 h) or zirconium-89 (89Zr; t1/2 = 3.3 days). Results obtained with 99mTc-ferucarbotran demonstrated that administration of fucoidan led to a 4-fold increase in the circulatory half-life (t1/2 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 89Zr-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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More information

Accepted/In Press date: 20 December 2017
e-pub ahead of print date: 17 January 2018
Published date: 27 February 2018
Keywords: dextran; ferucarbotran; fucoidan; positron emission tomography (PET); reticuloendothelial system (RES); single-photon emission computed tomography (SPECT); superparamagnetic iron oxide nanoparticles (SPIONs)

Identifiers

Local EPrints ID: 427817
URI: https://eprints.soton.ac.uk/id/eprint/427817
ISSN: 1936-0851
PURE UUID: 2415e3ea-003a-44a7-846b-ba49a324f554

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Date deposited: 29 Jan 2019 17:30
Last modified: 29 Jan 2019 17:30

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Contributors

Author: M.R.A. Abdollah
Author: T.J. Carter
Author: C. Jones
Author: T.L. Kalber
Author: V. Rajkumar
Author: B. Tolner
Author: C. Gruettner
Author: M. Zaw-Thin
Author: T. Baguña Torres
Author: M. Ellis
Author: M. Robson
Author: R.B. Pedley
Author: P. Mulholland
Author: R.T.M. de Rosales
Author: K.A. Chester

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