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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.


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TEM characterization of MnFe2O4 NPs and PEG-b-PCL-MnFe2CO4 NMs.Notes: MnFe2O4 NPs were of spheroidal appearance and narrow size distribution (A) and the average size was 7.6±1.0 nm (B). The diameter of PEG-b-PCL-MnFe2O4 NMs was 146.7±25.9 nm (C and D). Inset of (A) is SAED of MnFe2O4 NPs. Inset of (C) is an enlarged TEM of a single PEG-b-PCL-MnFe2O4 NM; magnification ×200,000.Abbreviations: NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone); SAED, selected area electron diffraction; TEM, transmission electron microscopy.
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f1-ijn-11-4051: TEM characterization of MnFe2O4 NPs and PEG-b-PCL-MnFe2CO4 NMs.Notes: MnFe2O4 NPs were of spheroidal appearance and narrow size distribution (A) and the average size was 7.6±1.0 nm (B). The diameter of PEG-b-PCL-MnFe2O4 NMs was 146.7±25.9 nm (C and D). Inset of (A) is SAED of MnFe2O4 NPs. Inset of (C) is an enlarged TEM of a single PEG-b-PCL-MnFe2O4 NM; magnification ×200,000.Abbreviations: NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone); SAED, selected area electron diffraction; TEM, transmission electron microscopy.

Mentions: MnFe2O4 NPs synthesized from thermal decomposition of iron acetylacetonate and manganese acetylacetonate in a 2:1 ratio were of spheroidal appearance and narrow size distribution (Figure 1A). The results from Image Pro Plus 6.0 showed that the average size was 7.6±1.0 nm (Figure 1B), as counted with 300 NPs that were randomly selected. After being enveloped with amphiphilic block copolymer PEG-b-PCL, dozens of hydrophobic MnFe2O4 NPs assembled together (Figure 1C). The diameter of PEG-b-PCL-MnFe2O4 was 146.7±25.9 nm according to the TEM photomicrograph (Figure 1D). Figure 2A and B show a high resolution TEM image of a single MnFe2O4 NP. The spacings between the lattice fringes were measured to be around 0.301 and 0.257 nm, which correspond to the planes of (220) and (311) of bulk MnFe2O4 very well. Moreover, the measured interplanar spacings based on the diffraction rings in the selected area electron diffraction (inset of Figure 1A) were perfectly in agreement with the respective hkl indexes of bulk MnFe2O4 from the Joint Committee on Powder Diffraction Standards (JCPDS) database, indicating that the synthetic NPs are MnFe2O4 nanocrystals. The chemical composition of the nanocrystals was confirmed using the energy dispersive spectrometer measurement. The Mn, Fe, and O peaks indicated the presence of Mn, Fe, and O in the NP (Figure 2C); meanwhile, the Cu signal is derived from the TEM grid. The atomic ratio of Fe to Mn was around 2:1, agreeing well with the molar ratio of Fe and Mn in MnFe2O4.


Targeting T 1 and T 2 dual modality enhanced magnetic resonance imaging of tumor vascular endothelial cells based on peptides-conjugated manganese ferrite nanomicelles
TEM characterization of MnFe2O4 NPs and PEG-b-PCL-MnFe2CO4 NMs.Notes: MnFe2O4 NPs were of spheroidal appearance and narrow size distribution (A) and the average size was 7.6±1.0 nm (B). The diameter of PEG-b-PCL-MnFe2O4 NMs was 146.7±25.9 nm (C and D). Inset of (A) is SAED of MnFe2O4 NPs. Inset of (C) is an enlarged TEM of a single PEG-b-PCL-MnFe2O4 NM; magnification ×200,000.Abbreviations: NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone); SAED, selected area electron diffraction; TEM, transmission electron microscopy.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4998025&req=5

f1-ijn-11-4051: TEM characterization of MnFe2O4 NPs and PEG-b-PCL-MnFe2CO4 NMs.Notes: MnFe2O4 NPs were of spheroidal appearance and narrow size distribution (A) and the average size was 7.6±1.0 nm (B). The diameter of PEG-b-PCL-MnFe2O4 NMs was 146.7±25.9 nm (C and D). Inset of (A) is SAED of MnFe2O4 NPs. Inset of (C) is an enlarged TEM of a single PEG-b-PCL-MnFe2O4 NM; magnification ×200,000.Abbreviations: NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone); SAED, selected area electron diffraction; TEM, transmission electron microscopy.
Mentions: MnFe2O4 NPs synthesized from thermal decomposition of iron acetylacetonate and manganese acetylacetonate in a 2:1 ratio were of spheroidal appearance and narrow size distribution (Figure 1A). The results from Image Pro Plus 6.0 showed that the average size was 7.6±1.0 nm (Figure 1B), as counted with 300 NPs that were randomly selected. After being enveloped with amphiphilic block copolymer PEG-b-PCL, dozens of hydrophobic MnFe2O4 NPs assembled together (Figure 1C). The diameter of PEG-b-PCL-MnFe2O4 was 146.7±25.9 nm according to the TEM photomicrograph (Figure 1D). Figure 2A and B show a high resolution TEM image of a single MnFe2O4 NP. The spacings between the lattice fringes were measured to be around 0.301 and 0.257 nm, which correspond to the planes of (220) and (311) of bulk MnFe2O4 very well. Moreover, the measured interplanar spacings based on the diffraction rings in the selected area electron diffraction (inset of Figure 1A) were perfectly in agreement with the respective hkl indexes of bulk MnFe2O4 from the Joint Committee on Powder Diffraction Standards (JCPDS) database, indicating that the synthetic NPs are MnFe2O4 nanocrystals. The chemical composition of the nanocrystals was confirmed using the energy dispersive spectrometer measurement. The Mn, Fe, and O peaks indicated the presence of Mn, Fe, and O in the NP (Figure 2C); meanwhile, the Cu signal is derived from the TEM grid. The atomic ratio of Fe to Mn was around 2:1, agreeing well with the molar ratio of Fe and Mn in MnFe2O4.

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.


Related in: MedlinePlus