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Glioma-targeting micelles for optical/magnetic resonance dual-mode imaging.

Zhou Q, Mu K, Jiang L, Xie H, Liu W, Li Z, Qi H, Liang S, Xu H, Zhu Y, Zhu W, Yang X - Int J Nanomedicine (2015)

Bottom Line: The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf).Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r 2) of micelles was 215.4 mM(-1)·s(-1), with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs.Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0-100 μg/mL.

View Article: PubMed Central - PubMed

Affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT
Surgical resection is the primary mode for glioma treatment, while gross total resection is difficult to achieve, due to the invasiveness of the gliomas. Meanwhile, the tumor-resection region is closely related to survival rate and life quality. Therefore, we developed optical/magnetic resonance imaging (MRI) bifunctional targeted micelles for glioma so as to delineate the glioma location before and during operation. The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf). Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r 2) of micelles was 215.4 mM(-1)·s(-1), with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs. The in vivo results indicated that the nanoparticles with Lf accumulated efficiently in glioma cells and prolonged the duration of hypointensity at the tumor site over 48 hours in the MR image compared to the nontarget group. Corresponding with the MRI results, the margin of the glioma was clearly demarcated in the fluorescence image, wherein the average fluorescence intensity of the tumor was about fourfold higher than that of normal brain tissue. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0-100 μg/mL. In general, these optical/MRI bifunctional micelles can specifically target the glioma and provide guidance for surgical resection of the glioma before and during operation.

No MeSH data available.


Related in: MedlinePlus

Ex vivo study of the brain tissue.Notes: (A) Ex vivo fluorescence images and H&E-staining images of rat brain bearing C6 glioma at 48 hours postinjection. (B) The average fluorescence intensity of the brain tumor and the normal brain. Results expressed as means ± standard error of mean (n=6).Abbreviations: Lf, lactoferrin; SPIO, superparamagnetic iron oxide; H&E, hematoxylin and eosin.
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f7-ijn-10-1805: Ex vivo study of the brain tissue.Notes: (A) Ex vivo fluorescence images and H&E-staining images of rat brain bearing C6 glioma at 48 hours postinjection. (B) The average fluorescence intensity of the brain tumor and the normal brain. Results expressed as means ± standard error of mean (n=6).Abbreviations: Lf, lactoferrin; SPIO, superparamagnetic iron oxide; H&E, hematoxylin and eosin.

Mentions: To test the capability of Cy5.5-Lf-SPIO micelles utilized as an optical contrast agent (Figure 7A), ex vivo NIR fluorescence images of the rats’ brains were analyzed by the IVIS Lumina XR system. As shown in Figure 7A, there was a distinct fluorescence signal in the middle of the brain obtained from the rats treated with Cy5.5-Lf-SPIO micelles. Abnormal cell density and morphology of tumor tissue were observed in the H&E-stained image (the purple part in the brain slice). H&E staining verified the location and the boundary of the brain tumor, which corresponded with the results from the NIR fluorescence images. However, for the negative group, there was no detectable fluorescence signal at the tumor site. The average fluorescence intensity of the brain-tumor tissue and the normal brain tissue was measured (Figure 7B). In the positive group, the average fluorescence intensity of the brain tumor was 3.8 times higher than that of normal brain tissue, which indicated that the NIR fluorescence was sensitive enough to discriminate the tumor tissue from the normal brain tissue.


Glioma-targeting micelles for optical/magnetic resonance dual-mode imaging.

Zhou Q, Mu K, Jiang L, Xie H, Liu W, Li Z, Qi H, Liang S, Xu H, Zhu Y, Zhu W, Yang X - Int J Nanomedicine (2015)

Ex vivo study of the brain tissue.Notes: (A) Ex vivo fluorescence images and H&E-staining images of rat brain bearing C6 glioma at 48 hours postinjection. (B) The average fluorescence intensity of the brain tumor and the normal brain. Results expressed as means ± standard error of mean (n=6).Abbreviations: Lf, lactoferrin; SPIO, superparamagnetic iron oxide; H&E, hematoxylin and eosin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356700&req=5

f7-ijn-10-1805: Ex vivo study of the brain tissue.Notes: (A) Ex vivo fluorescence images and H&E-staining images of rat brain bearing C6 glioma at 48 hours postinjection. (B) The average fluorescence intensity of the brain tumor and the normal brain. Results expressed as means ± standard error of mean (n=6).Abbreviations: Lf, lactoferrin; SPIO, superparamagnetic iron oxide; H&E, hematoxylin and eosin.
Mentions: To test the capability of Cy5.5-Lf-SPIO micelles utilized as an optical contrast agent (Figure 7A), ex vivo NIR fluorescence images of the rats’ brains were analyzed by the IVIS Lumina XR system. As shown in Figure 7A, there was a distinct fluorescence signal in the middle of the brain obtained from the rats treated with Cy5.5-Lf-SPIO micelles. Abnormal cell density and morphology of tumor tissue were observed in the H&E-stained image (the purple part in the brain slice). H&E staining verified the location and the boundary of the brain tumor, which corresponded with the results from the NIR fluorescence images. However, for the negative group, there was no detectable fluorescence signal at the tumor site. The average fluorescence intensity of the brain-tumor tissue and the normal brain tissue was measured (Figure 7B). In the positive group, the average fluorescence intensity of the brain tumor was 3.8 times higher than that of normal brain tissue, which indicated that the NIR fluorescence was sensitive enough to discriminate the tumor tissue from the normal brain tissue.

Bottom Line: The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf).Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r 2) of micelles was 215.4 mM(-1)·s(-1), with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs.Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0-100 μg/mL.

View Article: PubMed Central - PubMed

Affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

ABSTRACT
Surgical resection is the primary mode for glioma treatment, while gross total resection is difficult to achieve, due to the invasiveness of the gliomas. Meanwhile, the tumor-resection region is closely related to survival rate and life quality. Therefore, we developed optical/magnetic resonance imaging (MRI) bifunctional targeted micelles for glioma so as to delineate the glioma location before and during operation. The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf). Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r 2) of micelles was 215.4 mM(-1)·s(-1), with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs. The in vivo results indicated that the nanoparticles with Lf accumulated efficiently in glioma cells and prolonged the duration of hypointensity at the tumor site over 48 hours in the MR image compared to the nontarget group. Corresponding with the MRI results, the margin of the glioma was clearly demarcated in the fluorescence image, wherein the average fluorescence intensity of the tumor was about fourfold higher than that of normal brain tissue. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0-100 μg/mL. In general, these optical/MRI bifunctional micelles can specifically target the glioma and provide guidance for surgical resection of the glioma before and during operation.

No MeSH data available.


Related in: MedlinePlus