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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.


Hydrodynamic diameter of MnFe2O4 NPs and NMs.Notes: The hydrodynamic diameter of MnFe2O4 dispersed in hexane was 10.3±1.2 nm (A) and that of PEG-b-PCL-MnFe2O4 and CL-PEG-b-PCL-MnFe2O4 was 162.6±28.9 nm (B) and 183.4±26.5 (C), respectively.Abbreviations: NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone).
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f3-ijn-11-4051: Hydrodynamic diameter of MnFe2O4 NPs and NMs.Notes: The hydrodynamic diameter of MnFe2O4 dispersed in hexane was 10.3±1.2 nm (A) and that of PEG-b-PCL-MnFe2O4 and CL-PEG-b-PCL-MnFe2O4 was 162.6±28.9 nm (B) and 183.4±26.5 (C), respectively.Abbreviations: NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone).

Mentions: According to the results of dynamic light scattering, the hydrodynamic diameter of MnFe2O4 dispersed in hexane was 10.3±1.2 nm (Figure 3A), which was slightly larger than the size measured by TEM. This might be due to the coating of oleic acid or oleylamine on the outer surface of the NP that could affect the light scattering while it could not be detected under the TEM. Similarly, because of the hydrodynamic size effect and electronic permeability of the PEG-b-PCL, the zeta sizes of PEG-b-PCL-MnFe2O4 and CL-PEG-MnFe2O4 were 162.6±28.9 nm (Figure 3B) and 183.4±26.5 nm (Figure 3C), which were larger than those obtained from TEM observations. Inductive-coupled plasma optical emission spectrometer analysis showed that Fe and Mn elemental contents of MnFe2O4 were 363.5 and 167.9 mg/L, which matched the result of energy dispersive spectrometer analysis and revealed that the molar ratio of Fe and Mn of MnFe2O4 was ~2:1, indicating that the prepared NPs were 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
Hydrodynamic diameter of MnFe2O4 NPs and NMs.Notes: The hydrodynamic diameter of MnFe2O4 dispersed in hexane was 10.3±1.2 nm (A) and that of PEG-b-PCL-MnFe2O4 and CL-PEG-b-PCL-MnFe2O4 was 162.6±28.9 nm (B) and 183.4±26.5 (C), respectively.Abbreviations: NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone).
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4998025&req=5

f3-ijn-11-4051: Hydrodynamic diameter of MnFe2O4 NPs and NMs.Notes: The hydrodynamic diameter of MnFe2O4 dispersed in hexane was 10.3±1.2 nm (A) and that of PEG-b-PCL-MnFe2O4 and CL-PEG-b-PCL-MnFe2O4 was 162.6±28.9 nm (B) and 183.4±26.5 (C), respectively.Abbreviations: NMs, nanomicelles; NPs, nanoparticles; PEG-b-PCL, polyethylene glycol-block-poly(ε-caprolactone).
Mentions: According to the results of dynamic light scattering, the hydrodynamic diameter of MnFe2O4 dispersed in hexane was 10.3±1.2 nm (Figure 3A), which was slightly larger than the size measured by TEM. This might be due to the coating of oleic acid or oleylamine on the outer surface of the NP that could affect the light scattering while it could not be detected under the TEM. Similarly, because of the hydrodynamic size effect and electronic permeability of the PEG-b-PCL, the zeta sizes of PEG-b-PCL-MnFe2O4 and CL-PEG-MnFe2O4 were 162.6±28.9 nm (Figure 3B) and 183.4±26.5 nm (Figure 3C), which were larger than those obtained from TEM observations. Inductive-coupled plasma optical emission spectrometer analysis showed that Fe and Mn elemental contents of MnFe2O4 were 363.5 and 167.9 mg/L, which matched the result of energy dispersive spectrometer analysis and revealed that the molar ratio of Fe and Mn of MnFe2O4 was ~2:1, indicating that the prepared NPs were 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.