Limits...
Engineered biocompatible nanoparticles for in vivo imaging applications.

Chen S, Wang L, Duce SL, Brown S, Lee S, Melzer A, Cuschieri A, André P - J. Am. Chem. Soc. (2010)

Bottom Line: We describe the synthesis and characterization of a family of biocompatible FePt NPs suitable for biomedical applications, showing and discussing that FePt NPs can exhibit low cytotoxicity.The importance of engineering the interface of strongly magnetic NPs using a coating allowing free aqueous permeation is demonstrated to be an essential parameter in the design of new generations of diagnostic and therapeutic MRI contrast agents.This opens the way for several future applications of FePt NPs, including regenerative medicine and stem cell therapy in addition to enhanced MR diagnostic imaging.

View Article: PubMed Central - PubMed

Affiliation: School of Physics and Astronomy (SUPA), University of St Andrews, St Andrews KY16 9SS, UK.

ABSTRACT
Iron-platinum alloy nanoparticles (FePt NPs) are extremely promising candidates for the next generation of contrast agents for magnetic resonance (MR) diagnostic imaging and MR-guided interventions, including hyperthermic ablation of solid cancers. FePt has high Curie temperature, saturation magnetic moment, magneto-crystalline anisotropy, and chemical stability. We describe the synthesis and characterization of a family of biocompatible FePt NPs suitable for biomedical applications, showing and discussing that FePt NPs can exhibit low cytotoxicity. The importance of engineering the interface of strongly magnetic NPs using a coating allowing free aqueous permeation is demonstrated to be an essential parameter in the design of new generations of diagnostic and therapeutic MRI contrast agents. We report effective cell internalization of FePt NPs and demonstrate that they can be used for cellular imaging and in vivo MRI applications. This opens the way for several future applications of FePt NPs, including regenerative medicine and stem cell therapy in addition to enhanced MR diagnostic imaging.

Show MeSH

Related in: MedlinePlus

T2−1 (s−1) vs [Fe] (mM) of the water in 1% w/v agarose gel containing (blue ●) fcc-FePt-A, (green ▲) fcc-FePt-silica-A, and (orange ◆) Feridex (A1). 1H longitudinal relaxation time T2-weighted MRI images of 1% agarose gel/water solution containing fcc-FePt-A NPs with [Fe] = 0.00 mM (a), 0.02 mM (CFePt = 6 μg/mL) (b), and 0.04 mM (CFePt = 12 μg/mL) (c) (A2). T2-weighted cellular imaging by MRI (3D spin echo, TE = 30 ms, TR = 1 s) of A375M cells loaded with fcc-FePt-A NPs with a cell density of 10 × 103 cells/mL (a), 100 × 103 cells/mL (b), and 1000 × 103 cells/mL (c) (B). Embryo injected in ovo with cell culture media (1 μL) containing no NPs (C) and 20 μg/mL fcc-FePt-A (D). 3D surface reconstruction of embryo eyes (blue) and blood vessels (red) showing the position in yellow of the transverse and coronal images (C1,D1); dorsal view of transverse image of the embryo’s head aligned through the eyes (C2,D2); and anterior view of coronal image of the embryo’s head aligned through the eyes (C3,D3). 2D slices from 128 × 128 × 128 3D Rare-8 MRI data set of day 4 quail embryo egg (TR/TE = 250/25 ms), field of view of 30 mm and pixel dimensions of 0.234 mm/pixel. Labels: y, yolk; a, albumen; b, brain; in-e, injected eye; un-e, un-injected eye; h, heart. Scale bar indicates 1 mm. All the MRI measurements were completed at 7.1 T.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2962530&req=5

fig3: T2−1 (s−1) vs [Fe] (mM) of the water in 1% w/v agarose gel containing (blue ●) fcc-FePt-A, (green ▲) fcc-FePt-silica-A, and (orange ◆) Feridex (A1). 1H longitudinal relaxation time T2-weighted MRI images of 1% agarose gel/water solution containing fcc-FePt-A NPs with [Fe] = 0.00 mM (a), 0.02 mM (CFePt = 6 μg/mL) (b), and 0.04 mM (CFePt = 12 μg/mL) (c) (A2). T2-weighted cellular imaging by MRI (3D spin echo, TE = 30 ms, TR = 1 s) of A375M cells loaded with fcc-FePt-A NPs with a cell density of 10 × 103 cells/mL (a), 100 × 103 cells/mL (b), and 1000 × 103 cells/mL (c) (B). Embryo injected in ovo with cell culture media (1 μL) containing no NPs (C) and 20 μg/mL fcc-FePt-A (D). 3D surface reconstruction of embryo eyes (blue) and blood vessels (red) showing the position in yellow of the transverse and coronal images (C1,D1); dorsal view of transverse image of the embryo’s head aligned through the eyes (C2,D2); and anterior view of coronal image of the embryo’s head aligned through the eyes (C3,D3). 2D slices from 128 × 128 × 128 3D Rare-8 MRI data set of day 4 quail embryo egg (TR/TE = 250/25 ms), field of view of 30 mm and pixel dimensions of 0.234 mm/pixel. Labels: y, yolk; a, albumen; b, brain; in-e, injected eye; un-e, un-injected eye; h, heart. Scale bar indicates 1 mm. All the MRI measurements were completed at 7.1 T.

Mentions: The effectiveness of fcc-FePt-A and fcc-FePt-silica-A as MRI contrast agents was investigated by measuring the dependence of the longitudinal relaxation rate (T1−1) and transverse relaxation rate (T2−1) of 1% agarose gels.(43) Relaxivity (ri) quantifies the enhancement of either the longitudinal or the transverse relaxation rates of the protons in water. As expected at high magnetic field, the FePt NPs and Feridex have a weak influence on the water 1H longitudinal relaxation rate (Table 1 and SI-Figure 7A).16,43 In contrast, FePt NPs have a significant effect upon the aqueous transverse relaxation rate (Figure 3A1). The relaxivity r2 of the fcc-FePt-silica-A NPs is 40% larger than that of Feridex, which is attributed to the stronger magnetic moment of the fcc-FePt-silica-A NPs (SI-Figure 7B) at the MRI magnetic field (7 T).(43) Importantly, the relaxivity r2 of the fcc-FePt-A NPs is more than 6 times larger than that of Feridex. Figure 3A2 displays T2-weighted MRI images of various concentrations of fcc-FePt-A NPs in agarose gels. The signal intensity reduces and the image appears darker as the NPs concentration increases. The FePt NPs produce an observable change in image contrast at concentrations as low as 6 μg/mL, which is well within the safety range indicated by the cytotoxicity data (Figure 2A). Similarly, signal intensity loss was observed in cells labeled with fcc-FePt-A NPs as the cell density increases from 10 × 103 to 1000 × 103 cells/mL (Figure 3B).


Engineered biocompatible nanoparticles for in vivo imaging applications.

Chen S, Wang L, Duce SL, Brown S, Lee S, Melzer A, Cuschieri A, André P - J. Am. Chem. Soc. (2010)

T2−1 (s−1) vs [Fe] (mM) of the water in 1% w/v agarose gel containing (blue ●) fcc-FePt-A, (green ▲) fcc-FePt-silica-A, and (orange ◆) Feridex (A1). 1H longitudinal relaxation time T2-weighted MRI images of 1% agarose gel/water solution containing fcc-FePt-A NPs with [Fe] = 0.00 mM (a), 0.02 mM (CFePt = 6 μg/mL) (b), and 0.04 mM (CFePt = 12 μg/mL) (c) (A2). T2-weighted cellular imaging by MRI (3D spin echo, TE = 30 ms, TR = 1 s) of A375M cells loaded with fcc-FePt-A NPs with a cell density of 10 × 103 cells/mL (a), 100 × 103 cells/mL (b), and 1000 × 103 cells/mL (c) (B). Embryo injected in ovo with cell culture media (1 μL) containing no NPs (C) and 20 μg/mL fcc-FePt-A (D). 3D surface reconstruction of embryo eyes (blue) and blood vessels (red) showing the position in yellow of the transverse and coronal images (C1,D1); dorsal view of transverse image of the embryo’s head aligned through the eyes (C2,D2); and anterior view of coronal image of the embryo’s head aligned through the eyes (C3,D3). 2D slices from 128 × 128 × 128 3D Rare-8 MRI data set of day 4 quail embryo egg (TR/TE = 250/25 ms), field of view of 30 mm and pixel dimensions of 0.234 mm/pixel. Labels: y, yolk; a, albumen; b, brain; in-e, injected eye; un-e, un-injected eye; h, heart. Scale bar indicates 1 mm. All the MRI measurements were completed at 7.1 T.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2962530&req=5

fig3: T2−1 (s−1) vs [Fe] (mM) of the water in 1% w/v agarose gel containing (blue ●) fcc-FePt-A, (green ▲) fcc-FePt-silica-A, and (orange ◆) Feridex (A1). 1H longitudinal relaxation time T2-weighted MRI images of 1% agarose gel/water solution containing fcc-FePt-A NPs with [Fe] = 0.00 mM (a), 0.02 mM (CFePt = 6 μg/mL) (b), and 0.04 mM (CFePt = 12 μg/mL) (c) (A2). T2-weighted cellular imaging by MRI (3D spin echo, TE = 30 ms, TR = 1 s) of A375M cells loaded with fcc-FePt-A NPs with a cell density of 10 × 103 cells/mL (a), 100 × 103 cells/mL (b), and 1000 × 103 cells/mL (c) (B). Embryo injected in ovo with cell culture media (1 μL) containing no NPs (C) and 20 μg/mL fcc-FePt-A (D). 3D surface reconstruction of embryo eyes (blue) and blood vessels (red) showing the position in yellow of the transverse and coronal images (C1,D1); dorsal view of transverse image of the embryo’s head aligned through the eyes (C2,D2); and anterior view of coronal image of the embryo’s head aligned through the eyes (C3,D3). 2D slices from 128 × 128 × 128 3D Rare-8 MRI data set of day 4 quail embryo egg (TR/TE = 250/25 ms), field of view of 30 mm and pixel dimensions of 0.234 mm/pixel. Labels: y, yolk; a, albumen; b, brain; in-e, injected eye; un-e, un-injected eye; h, heart. Scale bar indicates 1 mm. All the MRI measurements were completed at 7.1 T.
Mentions: The effectiveness of fcc-FePt-A and fcc-FePt-silica-A as MRI contrast agents was investigated by measuring the dependence of the longitudinal relaxation rate (T1−1) and transverse relaxation rate (T2−1) of 1% agarose gels.(43) Relaxivity (ri) quantifies the enhancement of either the longitudinal or the transverse relaxation rates of the protons in water. As expected at high magnetic field, the FePt NPs and Feridex have a weak influence on the water 1H longitudinal relaxation rate (Table 1 and SI-Figure 7A).16,43 In contrast, FePt NPs have a significant effect upon the aqueous transverse relaxation rate (Figure 3A1). The relaxivity r2 of the fcc-FePt-silica-A NPs is 40% larger than that of Feridex, which is attributed to the stronger magnetic moment of the fcc-FePt-silica-A NPs (SI-Figure 7B) at the MRI magnetic field (7 T).(43) Importantly, the relaxivity r2 of the fcc-FePt-A NPs is more than 6 times larger than that of Feridex. Figure 3A2 displays T2-weighted MRI images of various concentrations of fcc-FePt-A NPs in agarose gels. The signal intensity reduces and the image appears darker as the NPs concentration increases. The FePt NPs produce an observable change in image contrast at concentrations as low as 6 μg/mL, which is well within the safety range indicated by the cytotoxicity data (Figure 2A). Similarly, signal intensity loss was observed in cells labeled with fcc-FePt-A NPs as the cell density increases from 10 × 103 to 1000 × 103 cells/mL (Figure 3B).

Bottom Line: We describe the synthesis and characterization of a family of biocompatible FePt NPs suitable for biomedical applications, showing and discussing that FePt NPs can exhibit low cytotoxicity.The importance of engineering the interface of strongly magnetic NPs using a coating allowing free aqueous permeation is demonstrated to be an essential parameter in the design of new generations of diagnostic and therapeutic MRI contrast agents.This opens the way for several future applications of FePt NPs, including regenerative medicine and stem cell therapy in addition to enhanced MR diagnostic imaging.

View Article: PubMed Central - PubMed

Affiliation: School of Physics and Astronomy (SUPA), University of St Andrews, St Andrews KY16 9SS, UK.

ABSTRACT
Iron-platinum alloy nanoparticles (FePt NPs) are extremely promising candidates for the next generation of contrast agents for magnetic resonance (MR) diagnostic imaging and MR-guided interventions, including hyperthermic ablation of solid cancers. FePt has high Curie temperature, saturation magnetic moment, magneto-crystalline anisotropy, and chemical stability. We describe the synthesis and characterization of a family of biocompatible FePt NPs suitable for biomedical applications, showing and discussing that FePt NPs can exhibit low cytotoxicity. The importance of engineering the interface of strongly magnetic NPs using a coating allowing free aqueous permeation is demonstrated to be an essential parameter in the design of new generations of diagnostic and therapeutic MRI contrast agents. We report effective cell internalization of FePt NPs and demonstrate that they can be used for cellular imaging and in vivo MRI applications. This opens the way for several future applications of FePt NPs, including regenerative medicine and stem cell therapy in addition to enhanced MR diagnostic imaging.

Show MeSH
Related in: MedlinePlus