In vitro multi-modal imaging of magnetic
targeted nanoparticles and their targeting effect on hepatic stellate cells

doi:10.3969/j.issn.2095-4344.2206

Abstract

Abstract:

BACKGROUND: In recent years, molecular imaging combined with medical imaging technology and targeted molecular probes have gradually become a research focus. The targeted tissues at the molecular level can be observed using molecular imaging, medical imaging technology, and targeted molecular probes in combination to realize non-invasive imaging of the occurrence and development of the diseases.

OBJECTIVE: To develop the magnetic targeted nanoparticle probes, observe the ultrasound/CT/MRI imaging properties in vitro, and investigate their targeting ability to rat hepatic stellate cells in vitro.

METHODS: Taking poly(lactic-co-glycolic acid) (PLGA) polymer as the shell, cyclic arginine-glycine-aspartic acid (cRGD) octapeptide as the ligand, targeted magnetic nanoparticles with superparamagnetic Fe₃O₄ embedded in the shell and perfluorooctyl bromide(PFOB) loaded in the core were prepared by double emulsion evaporation method. The physical and chemical properties of the nanoparticles were detected. The ultrasound/CT/MRI multi-modal imaging properties of the nanoparticles at different concentrations diluted with double-distilled water were tested in vitro. Cyclic RGD peptide immobilization on PLGA-Fe₃O₄-PFOB NPs was completed through the amide condensation reaction. The conjugation efficiency of the cRGD on PLGA-Fe₃O₄-PFOB NPs and targeting ability of targeted magnetic nanoparticles in vitro were verified. Cytotoxicity experiments were used to measure the toxic effects of nanoparticles at different concentrations on BRL-3A cells in each group.

RESULTS AND CONCLUSION: The targeted magnetic nanoparticles with the average size of (221.5±60.3) nm were uniform in dispersion and size. The prepared individual nanoparticle was spherical with the superparamagnetic Fe₃O₄ scattered on the shell. The encapsulation rate of Fe₃O₄ was 38%. In vitro ultrasound imaging and CT imaging signal decreased gradually as the concentrations of the nanoparticle suspension decreased. The T2-weighted signal of MRI decreased gradually with the increase of the concentrations of magnetic particle Fe₃O₄. Flow cytometry results showed that 94.13% of the cRGD was bound to the nanoparticles. In vitro cell targeting experiments showed that compared to PLGA-Fe₃O₄-PFOB NPs, cRGD-PLGA-Fe₃O₄-PFOB NPs exhibited greater cell targeting and affinity efficiency to hepatic stellate cells. Cytotoxicity experiments results showed the nanoparticles had no significant influence on cell viability of the BRL-3A cells. These results suggest that targeted magnetic nanoprobe cannot only be used as a multi-modal imaging contrast agent for ultrasound/CT/MRI, but also exhibits a strong specific affinity to rat hepatic stellate cells in vitro. It has great potential for the early diagnosis of liver fibrosis.

Key words: nanoparticles, target, contrast agent, multi-modal imaging, liver fibrosis, hepatic stellate cells, in vitro, molecular probes

CLC Number:

Li Xuan, Lu Min, Li Mingxing, Ao Meng, Tang Linmei, Zeng Zhen, Hu Jingwei, Huang Zhiqiang, Xuan Jiqing. In vitro multi-modal imaging of magnetic targeted nanoparticles and their targeting effect on hepatic stellate cells[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(4): 566-571.

Figures/Tables 7

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