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Targeting T 1 and T 2 dual modality enhanced magnetic resonance imaging of tumor vascular endothelial cells based on peptides-conjugated manganese ferrite nanomicelles

View Article: PubMed Central - PubMed

ABSTRACT

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T1/T2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T1 and T2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe2O4) nanoparticle core. The results showed that the hydrophobic MnFe2O4 nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM−1 s−1, which was much higher than that of MnFe2O4 nanoparticles (67.5 mM 1 s−1). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T2-weighted MR imaging. With the passage on, the Mn2+ ions were released from MnFe2O4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T1-weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe2O4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T1- and T2-enhanced MR imaging of tumor angiogenesis.

No MeSH data available.


MRI of MnFe2O4 TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs.Notes: TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs both exhibited a concentration-dependent signal drop in the GRE T2WI and FSE T2WI. The signal intensity decreased gradually with the increase of the metal ions concentration, while NMs induced greater hypointensity at an identical concentration compared with NPs.Abbreviations: MRI, magnetic resonance imaging; NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone); TMAH, tetramethylammonium hydroxide; T2WI, T2-weighted imaging; GRE, gradient echo; FSE, fast spin echo.
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f5-ijn-11-4051: MRI of MnFe2O4 TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs.Notes: TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs both exhibited a concentration-dependent signal drop in the GRE T2WI and FSE T2WI. The signal intensity decreased gradually with the increase of the metal ions concentration, while NMs induced greater hypointensity at an identical concentration compared with NPs.Abbreviations: MRI, magnetic resonance imaging; NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone); TMAH, tetramethylammonium hydroxide; T2WI, T2-weighted imaging; GRE, gradient echo; FSE, fast spin echo.

Mentions: To understand the magnetic property of the prepared MnFe2O4 NPs, 46.8 mg nanopowder was tested using a vibrating sample magnetometer. The magnetization rose nonlinearly with the increase of applied magnetic field (Figure 4A). The prepared NPs showed no remaining net magnetization in the absence of an external field, which indicated that the MnFe2O4 NPs were superparamagnetic at 300 K. Under a powerful magnetic field, NPs will reach their saturation magnetization, which was 68.2 emu/g. Figure 5 shows that TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs both exhibited a concentration-dependent signal drop in the GRE T2*WI and FSE T2-weighted imaging. Their signal intensities decreased gradually with the increase of the metal ion concentration. However, PEG-b-PCL-MnFe2O4 NMs induced greater hypointensity at an identical concentration compared with TMAH-MnFe2O4 NPs. The linear fitting of concentration and 1/T2 showed that the r2 of PEG-b-PCL-MnFe2O4 NMs was 281.7 mM−1 s−1, which was ~4.2 times higher than that of TMAH-MnFe2O4 4 NPs (67.5 mM− s−1) (Figure 4B).


Targeting T 1 and T 2 dual modality enhanced magnetic resonance imaging of tumor vascular endothelial cells based on peptides-conjugated manganese ferrite nanomicelles
MRI of MnFe2O4 TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs.Notes: TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs both exhibited a concentration-dependent signal drop in the GRE T2WI and FSE T2WI. The signal intensity decreased gradually with the increase of the metal ions concentration, while NMs induced greater hypointensity at an identical concentration compared with NPs.Abbreviations: MRI, magnetic resonance imaging; NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone); TMAH, tetramethylammonium hydroxide; T2WI, T2-weighted imaging; GRE, gradient echo; FSE, fast spin echo.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4998025&req=5

f5-ijn-11-4051: MRI of MnFe2O4 TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs.Notes: TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs both exhibited a concentration-dependent signal drop in the GRE T2WI and FSE T2WI. The signal intensity decreased gradually with the increase of the metal ions concentration, while NMs induced greater hypointensity at an identical concentration compared with NPs.Abbreviations: MRI, magnetic resonance imaging; NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone); TMAH, tetramethylammonium hydroxide; T2WI, T2-weighted imaging; GRE, gradient echo; FSE, fast spin echo.
Mentions: To understand the magnetic property of the prepared MnFe2O4 NPs, 46.8 mg nanopowder was tested using a vibrating sample magnetometer. The magnetization rose nonlinearly with the increase of applied magnetic field (Figure 4A). The prepared NPs showed no remaining net magnetization in the absence of an external field, which indicated that the MnFe2O4 NPs were superparamagnetic at 300 K. Under a powerful magnetic field, NPs will reach their saturation magnetization, which was 68.2 emu/g. Figure 5 shows that TMAH-MnFe2O4 NPs and PEG-b-PCL-MnFe2O4 NMs both exhibited a concentration-dependent signal drop in the GRE T2*WI and FSE T2-weighted imaging. Their signal intensities decreased gradually with the increase of the metal ion concentration. However, PEG-b-PCL-MnFe2O4 NMs induced greater hypointensity at an identical concentration compared with TMAH-MnFe2O4 NPs. The linear fitting of concentration and 1/T2 showed that the r2 of PEG-b-PCL-MnFe2O4 NMs was 281.7 mM−1 s−1, which was ~4.2 times higher than that of TMAH-MnFe2O4 4 NPs (67.5 mM− s−1) (Figure 4B).

View Article: PubMed Central - PubMed

ABSTRACT

Tumor angiogenesis plays very important roles for tumorigenesis, tumor development, metastasis, and prognosis. Targeting T1/T2 dual modality magnetic resonance (MR) imaging of the tumor vascular endothelial cells (TVECs) with MR molecular probes can greatly improve diagnostic sensitivity and specificity, as well as helping to make an early diagnosis of tumor at the preclinical stage. In this study, a new T1 and T2 dual modality nanoprobe was successfully fabricated. The prepared nanoprobe comprise peptides CL 1555, poly(ε-caprolactone)-block-poly(ethylene glycol) amphiphilic copolymer shell, and dozens of manganese ferrite (MnFe2O4) nanoparticle core. The results showed that the hydrophobic MnFe2O4 nanoparticles were of uniform spheroidal appearance and narrow size distribution. Due to the self-assembled nanomicelles structure, the prepared probes were of high relaxivity of 281.7 mM−1 s−1, which was much higher than that of MnFe2O4 nanoparticles (67.5 mM 1 s−1). After being grafted with the targeted CD105 peptide CL 1555, the nanomicelles can combine TVECs specifically and make the labeled TVECs dark in T2-weighted MR imaging. With the passage on, the Mn2+ ions were released from MnFe2O4 and the size decreased gradually, making the signal intensity of the second and third passage of labeled TVECs increased in T1-weighted MR imaging. Our results demonstrate that CL-poly(ethylene glycol)-MnFe2O4 can conjugate TVECs and induce dark and bright contrast in MR imaging, and act as a novel molecular probe for T1- and T2-enhanced MR imaging of tumor angiogenesis.

No MeSH data available.