Optimizing superparamagnetic iron oxide nanoparticles as drug carriers using an in vitro blood–brain barrier model

Figures & data

Figure 1 Cellular components of the blood–brain barrier (cross-sectional view).³

Notes: Adapted from Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacological Reviews. 2005;57(2):173–185. Copyright © 2005 by The American Society for Pharmacology and Experimental Therapeutics.³

Figure 2 Diagram of the in vitro BBB model.

Abbreviations: BBB, blood–brain barrier; b.End3, mouse brain endothelial cell.

Table 1 DLS and zeta potential of five SPION samples

SPION samples	Permeability (µg/mL)	Zeta potential (mV)	DLS (nm)
GGB	1.56	−68.9	192.08
GGC	1.8	−36.1	75.66
BPC	1.89	−29.0	17.02
GGP	1.9	−45.9	99.26
CPB	2.69	−43.3	105.78

Note: Reproduced from Shi D, Sun LL, Mi G, et al. Controlling ferrofluid permeability across the blood-brain barrier model. Nanotechnology. 2014;25(7):075101. © IOP Publishing. Reproduced with permission. All rights reserved.²¹

Abbreviations: BPC, bovine serum albumin, polyethylene glycol, and collagen; CPB, collagen, polyvinyl alcohol, and bovine serum albumin; DLS, dynamic light scattering; GGB, glycine, glutamic acid, and bovine serum albumin; GGC, glycine, glutamic acid, and collagen; GGP, glycine, glutamic acid, and polyvinyl alcohol; SPION, superparamagnetic iron oxide nanoparticle.

Figure 3 TEM image of the iron oxide core in GGC.

Notes: Magnification 75,000×. Reproduced from Shi D, Sun LL, Mi G, et al. Controlling ferrofluid permeability across the blood-brain barrier model. Nanotechnology. 2014; 25(7):075101. © IOP Publishing. Reproduced with permission. All rights reserved.²¹

Abbreviations: GGC, glycine, glutamine acid, and collagen; TEM, transmission electron microscopy.

Figure 4 XRD pattern of SPIONs.

Abbreviations: SPION, superparamagnetic iron oxide nanoparticle; XRD, X-ray diffraction.

Figure 5 Permeability of FITC-dextran across the cocultured BBB model.

Notes: Data are shown as the mean ± SD; N=3, *P<0.05 compared with 24 hours.

Abbreviations: BBB, blood–brain barrier; FITC, fluorescein isothiocyanate; SD, standard deviation.

Figure 6 Comparison of the TEER values between the two different BBB models.

Notes: Data are shown as the mean ± SD; N=3, *P<0.05 compared with the nonastrocyte-cultured BBB model.

Abbreviations: BBB, blood–brain barrier; SD, standard deviation; TEER, transendothelial electrical resistance.

Figure 7 Essential junction proteins expressed by b.End3 when cocultured with astrocytes.

Notes: Cells were stained with anti-ZO1-conjugated FITC (green) and counterstained with DAPI (blue). Magnification 40×.

Abbreviations: FITC, fluorescein isothiocyanate; b.End3, mouse brain endothelial cell.

Figure 8 Permeability of the SPIONs across the BBB model.

Notes: Data are shown as the mean ± SD; N=3, *P<0.05 compared with GGB.

Abbreviations: BBB, blood–brain barrier; BPC, bovine serum albumin, polyethylene glycol, and collagen; CPB, collagen, polyvinyl alcohol, and bovine serum albumin; GGB, glycine, glutamic acid, and bovine serum albumin; GGC, glycine, glutamic acid, and collagen; GGP, glycine, glutamic acid, and polyvinyl alcohol; SD, standard deviation; SPION, superparamagnetic iron oxide nanoparticle.

Figure 9 TEM thin sections of cell uptake of SPIONs.

Notes: (A) Cell uptake of CPB; magnification 3,000×. (B) Cell uptake of GGB; magnification 3,000×. (C–E) Endocytosis steps of cell uptaking CPB; (C and D) magnification 10,000×; (E) magnification 5,000×. (F) Exocytosis step of cell uptaking CPB; magnification 30,000×. The white circle and arrows in A and B indicate the SPIONs inside and attached to the cell. (C–F) Black arrows indicate SPIONs.

Abbreviations: CPB, collagen, polyvinyl alcohol, and bovine serum albumim; GGB, glycine, glutamic acid, and bovine serum albumin; SPION, superparamagnetic iron oxide nanoparticle; TEM, transmission electron microscopy.

Figure 10 Permeability of the four SPION samples (GGB, GGC, GGP, and BPC) by hydrodynamic diameter (DLS).

Abbreviations: BPC, bovine serum albumin, polyethylene glycol, and collagen; DLS, dynamic light scattering; GGB, glycine, glutamic acid, and bovine serum albumin; GGC, glycine, glutamic acid, and collagen; GGP, glycine, glutamic acid, and polyvinyl alcohol; SPION, superparamagnetic iron oxide nanoparticle.

Figure 11 Permeability of the four SPION samples (GGB, GGC, GGP, and BPC) by zeta potential.

Abbreviations: BPC, bovine serum albumin, polyethylene glycol, and collagen; GGB, glycine, glutamic acid, and bovine serum albumin; GGC, glycine, glutamic acid, and collagen; GGP, glycine, glutamic acid, and polyvinyl alcohol; SPION, super-paramagnetic iron oxide nanoparticle.

Figure 12 One-day cytotoxicity assay for SPION samples.

Notes: Data are shown as the mean ± SD; N=3. No statistical difference was observed.

Abbreviations: b.End3, mouse brain endothelial cell; SD, standard deviation; SPION, superparamagnetic iron oxide nanoparticle.

HawkinsBTDavisTPThe blood-brain barrier/neurovascular unit in health and diseasePharmacol Rev200557217318515914466

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ShiDSunLLMiGControlling ferrofluid permeability across the blood-brain barrier modelNanotechnology201425707510124457539

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