Fucoidan Prolongs the Circulation Time of Dextran-Coated Iron Oxide Nanoparticles

Abstract

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; t = 6 h) or zirconium-89 (Zr; t = 3.3 days). Results obtained with Tc-ferucarbotran demonstrated that administration of fucoidan led to a 4-fold increase in the circulatory half-life (t 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-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.

Discrepancies in the in vitro and in vivo role of scavenger receptors in clearance of nanoparticles by Kupffer cells

“…28,31 Another study demonstrated a strong effect of fucoidan, a polysulfated carbohydrate, on in vivo clearance of iron oxide nanoparticles. 32 Indeed, fucoidan is a broad inhibitor that blocks uptake via multiple classes of SRs (e.g., MARCO, PSOX, collectins, and LOX-1). 12,33 Adding to this complexity, polyanions interact with plasma and cell proteins, including complement, clotting factors, lipoproteins, and phospholipids.…”

Development and Characterization of a Fucoidan-Based Drug Delivery System by Using Hydrophilic Anticancer Polysaccharides to Simultaneously Deliver Hydrophobic Anticancer Drugs

“…In addition, several case studies of fucoidan as an alternative medicine in animal and human clinical trials have proved that combining fucoidan with clinical therapeutic agents can alleviate side effects of anti-cancer chemotherapy [ 21 , 23 ]. Recently, Abdollah et al [ 24 ] reported that fucoidan prolonged the circulation time of dextran-coated iron oxide nanoparticles (IONs) with a doubling in tumor uptake. Ikeguchi et al [ 25 ] examined the synergistic effect of a high-molecular-weight fucoidan with colorectal cancer chemotherapy agents, oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) or irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI).…”

<p>A New Pharmacokinetic Model Describing the Biodistribution of Intravenously and Intratumorally Administered Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in a GL261 Xenograft Glioblastoma Model</p>

“…To further validate the model two data sets from mice with intravenously injected SPIONs were analyzed. 39 The experimental data of both experiments could be described very well with the pharmacokinetic model (cf. Figure 3 ).…”

“…Radiolabeling of the nanoparticles with 89 Zr was performed as described previously. 39 Briefly, 35.6 MBq of Zirconium-89-oxalate ( 89 Zr 4+ in 1 M oxalic acid, PerkinElmer) was added to an Eppendorf tube with subsequent addition of Chelex-treated water (200 µL). The pH was raised to 8 employing 1 M Na 2 CO 3 (aq.).…”