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

Abstract

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 T2 relaxation 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.

Colorimetric hydrogen peroxide and glucose sensors based on the destruction of micelle-protected iron(ii) complex probes

“…As shown in Fig. 2A, the characteristics of the micelles are similar to that reported elsewhere, 41,42 where the colloidal sphere shapedparticles (average size of B0.89 AE 0.37 mm in diameter, as depicted in Fig. 2C) with a morphology of a small dark inner core of Fe 2+ -Dz complex surrounded by a thin light peripheral film outer shell of TX-114 surfactant were observed.…”

Novel targets for delaying aging: The importance of the liver and advances in drug delivery

“…A re cent study uti lized HA-bound nanopar ti cles in com bi na tion with gly cyrrhetinic acid (binds to gly cyrrhetinic acid re cep tors ex pressed on he pa to cytes) to pro mote tar get ing within the liver [172]. HA-drug con ju ga tion has been suc cess fully de vel oped for the de liv ery of an ticancer drugs to the liver [173,174]. also It has been pointed out that an ex ten sive range of sub strates (e.g.…”

“…How ever, Küpf fer cells and LSECs took up 50% of nanocrys tals mod i fied with DSPE-PEG that had a di am e ter of just 4-8 nm [183]. It ap pears that both the size and com po si tion of nanopar ti cles de ter mine which cell type is pref er en tially tar geted [174].…”

Multifunctional Traceable Liposomes with Temperature-Triggered Drug Release and Neovasculature-Targeting Properties for Improved Cancer Chemotherapy

“…A cyclic RGD peptide (cRGD) is a typical neovasculature-specific ligand. It has a high affinity for the α v β 3 integrin expressed on the surface of endothelial cells in tumor neovascular vessels. , Moreover, cRGD-containing polymeric micelles or liposomes can significantly improve the accumulation of these nanoparticles at the tumor site. − …”