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Gas vesicles (GVs) are gas-filled protein nanostructures that can regulate the buoyancy of microorganisms such as cyanobacteria and archaea. Recent studies have shown that GVs have the potential to be used as ultrasound molecular imaging probes in disease diagnosis and treatment. However, the mechanism of the inflation and deflation of GVs remains unclear, which hampers the preservation of GVs and gas replacement. In the present study, the environmental pH value was found to be an important factor in regulating the inflation and deflation of GVs. It can not only regulate the inflation and deflation of GVs in vivo to make Microcystis sp. cells present distinct levitation state, but also regulate the inflation and deflation of purified GVs in vitro, and the regulation process is reversible. Our results may provide a technical support for the large-scale production and preservation of biosynthetic ultrasound molecular imaging probes, especially for gas replacement to meet different diagnostic and therapeutic needs, and would facilitate the application of biosynthetic ultrasound molecular imaging probes.
Subject(s)
Cyanobacteria , Proteins/chemistry , Nanostructures/chemistry , Molecular Imaging , Hydrogen-Ion ConcentrationABSTRACT
Objective:To prepare cisplatin-loaded anti-progastrin-releasing peptide (ProGRP) monoclonal antibody targeted nanobubbles, and to explore the proliferation inhibition effect and anti-cancer molecular mechanism of them on small cell lung cancer (SCLC).Methods:The cisplatin targeted nanobubbles were prepared by thin film hydrating method, and the physicochemical property were explored. The subcutaneous xenograft tumor models of SCLC in 10 nude mice were established, and the ultrasound molecular targeting development effect of cisplatin targeted nanobubbles was analyzed by using blank nanobubbles as control. Another 24 tumor-bearing nude mouse models were established and randomly divided into four groups: blank nanobubbles group, cisplatin group, cisplatin nanobubbles group, cisplatin targeted nanobubbles group. The tumor inhibition rate was calculated. The effect on SCLC proliferation was detected by CCK8 method. RT-PCR and Western blotting methods were used to detect SCLC proliferation related genes the P53, Rb, c-myc protein and mRNA expression level of change, the molecular regulatory mechanism was analyzed.Results:The cisplatin targeted nanobubbles were successfully prepared. The particle size was (467.3±42.3)nm, the structure was stable. The cisplatin targeted nanobubbles had a good effect of ultrasonic molecular development in SCLC xenograft.Compared with the control group, the proliferation of SCLC cells was significantly inhibited by cisplatin targeted nanobubbles. The RT-PCR and Western blotting analysis showed that compared with the control group, the mRNA and protein levels of the proliferation-related gene P53 and Rb in the cisplatin targeted nanovesicles group were significantly up-regulated, and the mRNA and protein levels of c-myc were significantly down-regulated (all P<0.05). Conclusions:The cisplatin targeted nanobubbles can inhibit the proliferation of SCLC, and may be used as a new potential targeted drug for the treatment of SCLC.
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Carotid atherosclerotic plaque is closely related to the occurrence of ischemic stroke and coronary artery disease. Studies have shown that the vulnerability of carotid atherosclerotic plaque is one of the main causes of cardiovascular and cerebrovascular diseases, and its vulnerability is closely associated with the core of lipid necrosis, thin fibrous cap, high levels of macrophages, and intraplaque hemorrhage. With the advantages of easy operation, low cost, high safety and time -saving, ultrasound is more suitable than other imaging methods to become the routine screening method for the vulnerability of carotid atherosclerotic plaque. The article mainly introduces several emerging ultrasound technologies and their convenience and effectiveness, which are expected to detect the vulnerability of carotid atherosclerotic plaques in clinical practice.
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Ultrasound molecular imaging has become one of the hotspots of molecular imaging because of its advantages of non-invasion, non-radiation, repeatability and real-time dynamic imaging. The key of imaging is to select the appropriate target and ligand to bind to the ultrasound contrast agent. The formation of blood vessels in the development of tumor is a significant feature. Vascular endothelial growth factor receptor (VEGFR) is an important specific molecule on tumor vascular endothelial cells, and which can be used as a target for tumor ultrasound imaging. In recent years, many scholars have carried out related studies on the imaging of ultrasound molecules targeting VEGFR. This paper reviewed the mechanism and application of tumor ultrasound molecular imaging with VEGFR as target in recent years.
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Objective To prepare a novel ultrasound contrast agent , targeted phase-shift lipid nanoparticles mediated by tumor homing and penetrating peptide tLyP-1 ,and to evaluate its characteristics . Methods The nanoparticles were prepared by filming-rehydration and acoustic-vibration methods .The morphology ,distribution ,particle size and zeta potential were detected . After heating and irradiating of low intensity focused ultrasound ( LIFU) ,the phase-shift characteristic and the enhancement effect in vitro were observed . The tumor homing and cell-penetrating properties of the nanoparticles were examined by confocal laser scanning microscopy and flow cytometry . The cytotoxicity of the nanoparticles was evaluated by CCK 8 assay . Results The size and distribution of nanoparticles were uniformed . The size and zeta potential of nanoparticles were ( 399 .50 ± 29 .98) nm and ( 3 .28 ± 1 .72) mV ,respectively . When the nanoparticles were heated to a temperature of 45 ℃ or after irradiated by LIFU ,nanoparticles generated phase-shift and enhanced ultrasound imaging in vitro ( P 0 .05 ) . Conclusions A novel ultrasound contrast agent , targeted phase-shift lipid nanoparticles mediated by tumor homing and penetrating peptide tLyP-1 ,is prepared successfully . It can target to MDA-MB-231 cell and penetrate into the cell in vitro ,and enhance ultrasound imaging in vitro after LIFU irradiation ,which expected to become a novel tumor targeted ultrasound contrast agent and achieve ultrasound molecular imaging at the level of tumor cell .
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This paper summarizes the new progress of the research of the targeted microbubble ultrasound contrast agents and ultrasound molecular imaging in tumor angiogenesis.There are two constructing methods of targeted microbubble ultrasound contrast agents.Targeted new blood vessels microbubble unltrasound contrast agents are mainly divided into the connection of alpha(V)beta3 antibody,αVβ3 integration antibody and connecting VEGFR2.The quantitative analysis of targeted microbubble adhering to tumor target and the evaluation of the correlation between targeted microbubble adhering to tumor neovascular endothelial cell and tumor local pathological microvessel density suggest that ultrasound molecular imaging can be noninvasive,quick,repeated,dynamic and quantitative evaluate tumor angiogenesis and indirectly reflect the malignant tumor tissue proliferation activity and its biological characteristics.