In vitro multi-modal imaging of magnetic targeted nanoparticles and their targeting effect on hepatic stellate cells / 中国组织工程研究

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.