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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 (eRGO) 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 eRGO 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 eRGD 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. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a sonosensitizer-loaded multi-functional ultrasound (US) contrast agent for both tumour therapy and imaging. The hematoporphyrin (HP)-encapsulated poly(lactic-co-glycolic acid) microbubbles (HP-PLGA-MBs) were prepared and filled with perfluorocarbon gases. The enhancement of US imaging and its sonodynamically induced anti-tumour effect were evaluated by both in vitro and in vivo experiments. The HP-PLGA-MBs have a narrow size distribution and smooth surface with a mean diameter of 702.6 ± 56.8 nm and HP encapsulation efficiency of 63.50 ± 1.26% and drug-loading efficiency of 2.15 ± 0.13%. The HP-PLGA-MBs could well enhance the ultrasound imaging both in vitro and in vivo. A significant anti-tumour effect was obtained by HP-PLGA-MBs mediated sonodynamic therapy. The tumour growth rate and the tumour proliferation index were the lowest in the HP-PLGA-MBs plus sonication group. And the tumour cell apoptotic index was the biggest in the HP-PLGA-MBs plus sonication group. In conclusion, a sonosensitizer-loaded multi-functional contrast agent was constructed and the feasibility was demonstrated, which might provide a novel strategy for tumour imaging and therapy. [ABSTRACT FROM AUTHOR]

Objective: To prepare the Gd‐DTPA‐loaded poly (lactic‐co‐glycolic acid) (PLGA) microbubbles for both ultrasound imaging and MRI imaging. Methods: Biodegradable high‐molecular‐weight poly (lactic‐co‐glycolic acid) (PLGA) was used as an encapsulating vehicle to fabricate a contrast agent composed of gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) and fluorocarbon‐filled microbubbles by using double emulsion method. The morphology, size, and Gd loading capacity of PLGA microparticles were assessed. The efficacy of the contrast agent for ultrasound and magnetic resonance (MR) imaging was evaluated by in vivo imaging of hepatic vessels and the liver parenchyma of rabbit following injection of the contrast agent. Additionally, the liver and kidney functions were examined before and at 7, 14, 30 days after injection. Results: Electron microscopy showed Gd loaded PLGA microbubbles were spherical in shape. The mean diameter were 1.47 ± 0.38 μm and the Gd loading was 25 ± 2 μg/mg. Right after the injection of the PLGA microbubbles, the ultrasound echo intensity of hepatic vessels and the liver parenchyma was significantly enhanced. Moreover, enhanced signal intensity of the liver parenchyma on MR images was observed for ∼30 min after injection of the contrast agent. Neither marked changes in the liver and kidney functions nor other severe complications were detected during the follow‐up period. Conclusion: Gd‐DTPA‐loaded PLGA microbubbles could enhance both ultrasound imaging and MRI imaging. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. [ABSTRACT FROM AUTHOR]