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Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide nanoparticles for targeting and magnetic resonance imaging of breast cancer.

Chen H, Wang L, Yu Q, Qian W, Tiwari D, Yi H, Wang AY, Huang J, Yang L, Mao H - Int J Nanomedicine (2013)

Bottom Line: Antifouling magnetic iron oxide nanoparticles (IONPs) coated with block copolymer poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane) (PEO-b-PγMPS) were investigated for improving cell targeting by reducing nonspecific uptake.Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv) of antibody against epidermal growth factor receptor (ScFvEGFR) to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs).On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Imaging Sciences, Atlanta, GA.

ABSTRACT
Antifouling magnetic iron oxide nanoparticles (IONPs) coated with block copolymer poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane) (PEO-b-PγMPS) were investigated for improving cell targeting by reducing nonspecific uptake. Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv) of antibody against epidermal growth factor receptor (ScFvEGFR) to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs). The anti-HER2-IONPs bound specifically to SK-BR-3, a HER2-overexpressing breast cancer cell line, but not to MDA-MB-231, a HER2-underexpressing cell line. On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line. Transmission electron microscopy revealed internalization of the receptor-targeted nanoparticles by the targeted cancer cells. In addition, both antibody-conjugated and non-antibody-conjugated IONPs showed reduced nonspecific uptake by RAW264.7 mouse macrophages in vitro. The developed IONPs showed a long blood circulation time (serum half-life 11.6 hours) in mice and low accumulation in both the liver and spleen. At 24 hours after systemic administration of ScFvEGFR-IONPs into mice bearing EGFR-positive breast cancer 4T1 mouse mammary tumors, magnetic resonance imaging revealed signal reduction in the tumor as a result of the accumulation of the targeted IONPs.

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(A) Serum half-life of nanoparticles after tail vein injection of 10 mg Fe/kg of mouse body weight (open squares), where iron concentration was measured by spectrophotometry. Triangle represents serum iron concentration in noninjected control mice. The error bar is the standard deviation with four mice in each time point. (B) Biodistribution of PEO-b-PγMPS-coated IONPs in the major organs of BALB/c mice, including liver, spleen, kidney, lung, brain, and muscle. The data were recorded from the whole organ taken at indicated time points after tail vein injection and were determined by spectrophotometry. Each group contains four mice, and the error bar is the standard deviation.Abbreviations: IONPs, iron oxide nanoparticles; PEO-b-PγMPS, poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane); h, hours.
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f5-ijn-8-3781: (A) Serum half-life of nanoparticles after tail vein injection of 10 mg Fe/kg of mouse body weight (open squares), where iron concentration was measured by spectrophotometry. Triangle represents serum iron concentration in noninjected control mice. The error bar is the standard deviation with four mice in each time point. (B) Biodistribution of PEO-b-PγMPS-coated IONPs in the major organs of BALB/c mice, including liver, spleen, kidney, lung, brain, and muscle. The data were recorded from the whole organ taken at indicated time points after tail vein injection and were determined by spectrophotometry. Each group contains four mice, and the error bar is the standard deviation.Abbreviations: IONPs, iron oxide nanoparticles; PEO-b-PγMPS, poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane); h, hours.

Mentions: The blood retention time and biodistribution of PEO-b-PγMPS-coated IONPs was investigated by measuring the iron concentrations in serum and selected organs at various time points after intravenous injection of a dose of 10 mg Fe/kg (mouse body weight) of IONPs in mice (n = 4 per time point). Iron concentration was determined by spectrophotometry (Figure S2). Figure 5A shows a plot of the time-dependent change in mean serum iron concentration. The mean iron concentration in mouse serum at 15 minutes after injection of IONPs was 0.323 ± 0.039 mg Fe/g, which was 6.9 times higher than that (0.047 ± 0.009 mg Fe/g) in the control mice not receiving IONPs, followed by gradual clearance of nanoparticles from the blood. Forty-eight hours after injection of PEO-b-PγMPS-coated IONPs, the iron concentration in serum approached the background level of 0.059 ± 0.014 mg Fe/g. By fitting iron concentrations obtained at different time points to a monoexponential decay model, an estimated serum half-life (t1/2) of 11.6 hours (R2 = 0.993) was obtained for PEO-b-PγMPS diblock copolymer-coated IONPs. This blood half-time is in the range generally considered optimal for nanoparticles to reach and accumulate in the target tumor tissue.47


Anti-HER2 antibody and ScFvEGFR-conjugated antifouling magnetic iron oxide nanoparticles for targeting and magnetic resonance imaging of breast cancer.

Chen H, Wang L, Yu Q, Qian W, Tiwari D, Yi H, Wang AY, Huang J, Yang L, Mao H - Int J Nanomedicine (2013)

(A) Serum half-life of nanoparticles after tail vein injection of 10 mg Fe/kg of mouse body weight (open squares), where iron concentration was measured by spectrophotometry. Triangle represents serum iron concentration in noninjected control mice. The error bar is the standard deviation with four mice in each time point. (B) Biodistribution of PEO-b-PγMPS-coated IONPs in the major organs of BALB/c mice, including liver, spleen, kidney, lung, brain, and muscle. The data were recorded from the whole organ taken at indicated time points after tail vein injection and were determined by spectrophotometry. Each group contains four mice, and the error bar is the standard deviation.Abbreviations: IONPs, iron oxide nanoparticles; PEO-b-PγMPS, poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane); h, hours.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3794963&req=5

f5-ijn-8-3781: (A) Serum half-life of nanoparticles after tail vein injection of 10 mg Fe/kg of mouse body weight (open squares), where iron concentration was measured by spectrophotometry. Triangle represents serum iron concentration in noninjected control mice. The error bar is the standard deviation with four mice in each time point. (B) Biodistribution of PEO-b-PγMPS-coated IONPs in the major organs of BALB/c mice, including liver, spleen, kidney, lung, brain, and muscle. The data were recorded from the whole organ taken at indicated time points after tail vein injection and were determined by spectrophotometry. Each group contains four mice, and the error bar is the standard deviation.Abbreviations: IONPs, iron oxide nanoparticles; PEO-b-PγMPS, poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane); h, hours.
Mentions: The blood retention time and biodistribution of PEO-b-PγMPS-coated IONPs was investigated by measuring the iron concentrations in serum and selected organs at various time points after intravenous injection of a dose of 10 mg Fe/kg (mouse body weight) of IONPs in mice (n = 4 per time point). Iron concentration was determined by spectrophotometry (Figure S2). Figure 5A shows a plot of the time-dependent change in mean serum iron concentration. The mean iron concentration in mouse serum at 15 minutes after injection of IONPs was 0.323 ± 0.039 mg Fe/g, which was 6.9 times higher than that (0.047 ± 0.009 mg Fe/g) in the control mice not receiving IONPs, followed by gradual clearance of nanoparticles from the blood. Forty-eight hours after injection of PEO-b-PγMPS-coated IONPs, the iron concentration in serum approached the background level of 0.059 ± 0.014 mg Fe/g. By fitting iron concentrations obtained at different time points to a monoexponential decay model, an estimated serum half-life (t1/2) of 11.6 hours (R2 = 0.993) was obtained for PEO-b-PγMPS diblock copolymer-coated IONPs. This blood half-time is in the range generally considered optimal for nanoparticles to reach and accumulate in the target tumor tissue.47

Bottom Line: Antifouling magnetic iron oxide nanoparticles (IONPs) coated with block copolymer poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane) (PEO-b-PγMPS) were investigated for improving cell targeting by reducing nonspecific uptake.Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv) of antibody against epidermal growth factor receptor (ScFvEGFR) to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs).On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Imaging Sciences, Atlanta, GA.

ABSTRACT
Antifouling magnetic iron oxide nanoparticles (IONPs) coated with block copolymer poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane) (PEO-b-PγMPS) were investigated for improving cell targeting by reducing nonspecific uptake. Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv) of antibody against epidermal growth factor receptor (ScFvEGFR) to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs). The anti-HER2-IONPs bound specifically to SK-BR-3, a HER2-overexpressing breast cancer cell line, but not to MDA-MB-231, a HER2-underexpressing cell line. On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line. Transmission electron microscopy revealed internalization of the receptor-targeted nanoparticles by the targeted cancer cells. In addition, both antibody-conjugated and non-antibody-conjugated IONPs showed reduced nonspecific uptake by RAW264.7 mouse macrophages in vitro. The developed IONPs showed a long blood circulation time (serum half-life 11.6 hours) in mice and low accumulation in both the liver and spleen. At 24 hours after systemic administration of ScFvEGFR-IONPs into mice bearing EGFR-positive breast cancer 4T1 mouse mammary tumors, magnetic resonance imaging revealed signal reduction in the tumor as a result of the accumulation of the targeted IONPs.

Show MeSH
Related in: MedlinePlus