A novel human artery model to assess the magnetic accumulation of SPIONs under flow conditions

Figures

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  Figure 1. Umbilical artery model. (A) Umbilical artery embedded in agarose gel; (B) Schematic presentation of the experimental set-up for magnetic targeting; (C) Example image showing the electromagnet, the artery, SPION reservoir, and peristaltic pump. Red arrows indicate the flow direction.

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  Figure 2. Magnetic targeting of circulating SPION-1. (A) SPION-1 suspension at 30 μg Fe/mL was circulated for 30 min under external magnetic field gradient positioned at segment “0” (red bars; the magnetic field gradient at the centre of artery: 40 T/m) or without magnetic force (green bars). Shown is iron concentration of respective segments (mean values ± SEM of n = 5 experiments). ***P < 0.001; **P < 0.01 vs region “0” under the tip of the magnet; ##P < 0.01 vs corresponding targeted region. (B) Representative images from n = 3 experiments corresponding to the artery segments −1, 0 and +1. Iron accumulation, visualised with Prussian blue staining, is highlighted with arrows.

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  Figure 3. Magnetic targeting of circulating SPION-2 and SPION-3. (A) SPION-2 and (B) SPION-3 suspensions at 30 μg Fe/mL were circulated in the model for 30 min under external magnetic force positioned at segment “0” (grey bars; the magnetic field gradient at the centre of artery: 40 T/m) or without magnetic force (black bars). Shown is iron concentration of respective segments (mean values ± SEM of n = 5 experiments). **P < 0.01, *P < 0.05, ns – two-tailed P value of 0.097 vs region “0”; ##P < 0.01, #P < 0.05 vs corresponding targeted region.

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  Figure 4. Histological evaluation of magnetic targeting. Representative images from n = 3 experiments corresponding to the artery segments 0, +1 and +4 are shown for (A) SPION-2 and (B) SPION-3. Iron accumulation, visualized with Prussian blue staining, is highlighted with arrows. No accumulation was detectable by histology in the analysed SPION-3 samples.

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  Figure 5. Effect of magnetic field parameters on magnetic targeting. SPION-1 suspension at 30 μg Fe/mL was circulated in the model for 30 min. The estimated magnetic field gradient at the centre of artery lumen was 40 T/m (grey bars) or 30 T/m (striped bars). In further experiments, tip of the magnet set to 72 T/m was positioned at 1 cm distance from agarose gel surface (total distance from the artery: 15 mm; 16 T/m at the centre of artery lumen; black bars). Shown is the iron concentration of respective segments (mean values ± SEM of n = 5 experiments). **P < 0.01, *P < 0.05 vs respective region “0”; ‡P < 0.05 vs region “0” at 40 T/m. The P values in “+1 cm” samples versus corresponding regions at 30 T/m are indicated.

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  Figure 6. Effects of time and flow rate on magnetic targeting of circulating SPIONs. SPION-1 suspension at 30 μg Fe/mL was circulated for 30 min (grey bars) or 60 min (black bars). The magnetic field gradient at the centre of artery was 40 T/m. In further experiments, flow rate was reduced to 2.4 mL/min (striped bars). Shown is the iron concentration of respective segments (mean values ± SEM of n = 5 experiments). **P < 0.01, *P < 0.05 vs respective region “0”; ns, two-tailed P value = 0.16 vs region “0” at flow rate of 4.8 mL/min.