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Synthesis and in vitro experiments of carcinoma vascular endothelial targeting polymeric nano-micelles combining small particle size and supermagnetic sensitivity

文献作者：Yi Zhang, Jielin Pan, Qilan Xu, Hao Li, Jianhao Wang, Chao Zhang, and Guobin Hong   《International Journal of Medical Sciences》

ABSTRACTS
Objective: To construct carcinoma vascular endothelial-targeted polymeric nanomicelles with high magnetic resonance imaging (MRI) sensitivity and to evaluate their biological safety and in vitro tumor-targeting effect, and to monitor their feasibility using clinical MRI scanner.
Method: Amphiphilic block copolymer, poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) was synthesized via the ring-opening polymerization of ε-caprolactone (CL) initiated by poly(ethylene glycol) (PEG), in which cyclic pentapeptide Arg-Gly-Asp (cRGD) was conjugated with the terminal of hydrophilic PEG block. During the self-assembly of PEG-PCL micelles, superparamagnetic γ-Fe2O3 nanoparticles (11 nm) was loaded into the hydrophobic core. The cRGD-terminated γ-Fe2O3-loaded polymeric micelles targeting to carcinoma vascular endothelial cells, were characterized in particle size, morphology, loading efficiency and so on, especially high MRI sensitivity in vitro. Normal hepatic vascular endothelial cells (ED25) were incubated with the resulting micelles for assessing their safety. Human hepatic carcinoma vascular endothelial cells (T3A) were cultured with the resulting micelles to assess the micelle uptake using Prussian blue staining and the cell signal intensity using MRI.
Results: All the polymeric micelles exhibited ultra-small particle sizes with approximately 50 nm, high relaxation rate, and low toxicity even at high iron concentrations. More blue-stained iron particles were present in the targeting group than the non-targeting and competitive inhibition groups. In vitro MRI showed T2WI and T2relaxation times were significantly lower in the targeting group than in the other two groups.
Conclusion: γ-Fe2O3-loaded PEG-PCL micelles not only possess ultra-small size and high superparamagnetic sensitivity, also can be actively targeted to carcinoma vascular endothelial cells by tumor-targeted cRGD. It appears to be a promising contrast agent for tumor-targeted imaging.
KEY WORDS
micelles, PEG-PCL, cRGD, γ-Fe2O3, MRI
SCREENSHOT

RELATED PRODUCTS
Cyclic pentapeptide Arg-Gly-Asp (cRGD, 95%) was purchased from Chinapeptides Co., Ltd., China. 
CHAINING
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859773/
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