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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.

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ROS of TVECs labeled with CL-PEG-MnFe2O4.Notes: The ROS levels of TVECs labeled with 0.05 (B), 0.23 (C), 0.45 (D), and 0.9 (E) mM CL-PEG-MnFe2O4 solutions were very low and depicted an insignificant elevation of ROS level compared with the control (A). However, a 3.18% higher intracellular ROS level was measured in the cells incubated with 4.5 mM CL-PEG-MnFe2O4 solution compared with 0.9 mM CL-PEG-MnFe2O4 (F).Abbreviations: PEG, poly(ethylene glycol); ROS, reactive oxygen species; TVECs, tumor vascular endothelial cells.
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f7-ijn-11-4051: ROS of TVECs labeled with CL-PEG-MnFe2O4.Notes: The ROS levels of TVECs labeled with 0.05 (B), 0.23 (C), 0.45 (D), and 0.9 (E) mM CL-PEG-MnFe2O4 solutions were very low and depicted an insignificant elevation of ROS level compared with the control (A). However, a 3.18% higher intracellular ROS level was measured in the cells incubated with 4.5 mM CL-PEG-MnFe2O4 solution compared with 0.9 mM CL-PEG-MnFe2O4 (F).Abbreviations: PEG, poly(ethylene glycol); ROS, reactive oxygen species; TVECs, tumor vascular endothelial cells.

Mentions: The relative cell viability (RCV) of each treatment group to control group was used to determine the cytotoxicity of CL-PEG-MnFe2O4 and MnCl2 with different concentrations on TVECs. Figure 6 shows that the RCV of TVECs labeled with CL-PEG-MnFe2O4 within 0.9 mM decreased only 7%–9% compared to controls. As the concentration increased, the RCV decreased correspondingly, and a decrease of ~19% in viability of TVECs incubated with 4.5 mM CL-PEG-MnFe2O4 solution was measured. On the contrary, a notable decrease of ~15% in viability was observed in TVECs incubated with only 0.05 mM MnCl2 solution. When the TVECs were incubated with MnCl2 solution as high as 4.5 mM, there were only 36.2% cells that survived. The CCK-8 results demonstrated that the CL-PEG-MnFe2O4 showed no acute toxicity to TVECs even at high concentrations, indicating their much better biocompatibility than molecular manganese agents. The ROS level of TVECs labeled with 0, 0.05, 0.23, 0.45, 0.9, and 4.5 mM CL-PEG-MnFe2O4 solutions are shown in Figure 7. It was shown that the induction of ROS depended on the concentration and an insignificant ROS level elevation was detected in the cells exposed to CL-PEG-MnFe2O4 within 0.9 mM. However, a 3.18% higher intracellular ROS level was measured in the cells incubated with 4.5 mM CL-PEG-MnFe2O4 solution compared with 0.9 mM CL-PEG-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
ROS of TVECs labeled with CL-PEG-MnFe2O4.Notes: The ROS levels of TVECs labeled with 0.05 (B), 0.23 (C), 0.45 (D), and 0.9 (E) mM CL-PEG-MnFe2O4 solutions were very low and depicted an insignificant elevation of ROS level compared with the control (A). However, a 3.18% higher intracellular ROS level was measured in the cells incubated with 4.5 mM CL-PEG-MnFe2O4 solution compared with 0.9 mM CL-PEG-MnFe2O4 (F).Abbreviations: PEG, poly(ethylene glycol); ROS, reactive oxygen species; TVECs, tumor vascular endothelial cells.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4998025&req=5

f7-ijn-11-4051: ROS of TVECs labeled with CL-PEG-MnFe2O4.Notes: The ROS levels of TVECs labeled with 0.05 (B), 0.23 (C), 0.45 (D), and 0.9 (E) mM CL-PEG-MnFe2O4 solutions were very low and depicted an insignificant elevation of ROS level compared with the control (A). However, a 3.18% higher intracellular ROS level was measured in the cells incubated with 4.5 mM CL-PEG-MnFe2O4 solution compared with 0.9 mM CL-PEG-MnFe2O4 (F).Abbreviations: PEG, poly(ethylene glycol); ROS, reactive oxygen species; TVECs, tumor vascular endothelial cells.
Mentions: The relative cell viability (RCV) of each treatment group to control group was used to determine the cytotoxicity of CL-PEG-MnFe2O4 and MnCl2 with different concentrations on TVECs. Figure 6 shows that the RCV of TVECs labeled with CL-PEG-MnFe2O4 within 0.9 mM decreased only 7%–9% compared to controls. As the concentration increased, the RCV decreased correspondingly, and a decrease of ~19% in viability of TVECs incubated with 4.5 mM CL-PEG-MnFe2O4 solution was measured. On the contrary, a notable decrease of ~15% in viability was observed in TVECs incubated with only 0.05 mM MnCl2 solution. When the TVECs were incubated with MnCl2 solution as high as 4.5 mM, there were only 36.2% cells that survived. The CCK-8 results demonstrated that the CL-PEG-MnFe2O4 showed no acute toxicity to TVECs even at high concentrations, indicating their much better biocompatibility than molecular manganese agents. The ROS level of TVECs labeled with 0, 0.05, 0.23, 0.45, 0.9, and 4.5 mM CL-PEG-MnFe2O4 solutions are shown in Figure 7. It was shown that the induction of ROS depended on the concentration and an insignificant ROS level elevation was detected in the cells exposed to CL-PEG-MnFe2O4 within 0.9 mM. However, a 3.18% higher intracellular ROS level was measured in the cells incubated with 4.5 mM CL-PEG-MnFe2O4 solution compared with 0.9 mM CL-PEG-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