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Objective To explore the mechanism that gold nanorods trigger apoptosis in cancer cells.Methods Gold nanorods was synthesized by gold seed growing method, and its characterization was detected; gold nanorods on cell proliferation-toxicity were evaluated by CCK-8 Kit and apoptosis were detected by flow; mitochondrial membrane potential were tested by JC-1 and activation of Caspase 9 and Caspase 3 were detected by western blot. Results The results found that gold nanorods had nontoxic to normal cells, but highly toxic to tumor cells; and with the increasing of gold nanorods’ working time, the percentage of apoptotic cancer cells was increasing; in addition to, normal cells’ mitochondrial membrane potential did not change, but cancer cells had a significant reduction in mitochondrial membrane potential.Conclusion This study proves that gold nanorods induce apoptosis through the mitochondrial apoptosis pathway.
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With the rapid development of nanotechnology, nano oncology medicine that is formed through the combination of nano science and oncology medicine has become an important field emerging in nano science. Because of its unique optical properties, the gold nanorod (GNR), that is a rod-shaped nano materials, has shown great potential applications in the biomedical field, especially, in GRNs thermotherapy, radio-sensitizing effect therapy and targeting therapy of the tumor. Being a newly-developed therapy, gold nanorods combined with internal radiotherapy has already obtained excellent durative effect in targeting therapy of tumor. This paper aims to make a comprehensive review about its mechanism and its clinical application and research situation in recent years.
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Objective To establish the rabbit model with hepatic VX-2 tumor and to investigate the intake of folate-conjugated silica-coated gold nanorods (GNRs@SiO2-FA) in experimental rabbits. Methods Under CT-guidance, animal model with VX-2 liver cancer was established in 27 rabbits by using puncture inoculation method. CT scanning and sonography were employed to observe the tumor growth. After two weeks, the rabbits were randomly and equally divided into blank control group (n=9, injection of saline), portal vein injection group (n=9, injection of GNRs@SiO2-FA) and intra-tumoral injection group (n=9, injection of GNRs@SiO2-FA). Every three rabbits from each group were sacrificed each time at 24 h, 48 h and 72 h after the treatment. The tumor tissue and the major organs were collected and sent for pathological examination. The cellular uptake of GNRs@SiO2-FA was studied by confocal laser scanning microscopy. Results The rabbit model of VX-2 liver cancer was successfully established. CT and sonography examination indicated that the tumor was rich in blood supply. Confocal laser scanning microscopy revealed that GNRs@SiO2-FA could specifically bind with tumor cells within 24 hours after injection, then the GNRs@SiO2-FA entered into the tumor cells and gathered in the tumor cytoplasm. Conclusion GNRs@SiO2-FA has highly targeted effect on the liver cancer cells in experimental animals, which has very important application prospect in targeting hyperthermia therapy and in 125I seed implantation therapy.
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Objective To explore the possible mechanism of the apoptosis of hepatoma cell line HepG2 induced by the combination use of GNRs@SiO2-FA and 125I seeds and to discuss its relationship with Bcl-2 and Bax protein expressions so as to provide theoretical basis for clinical treatment of hepatic cancer with interstitial brachytherapy by using 125I seeds. Methods In vitro cultured HepG2 cells were randomly divided into 4 groups: blank control group (not treated), simple GNRs@SiO2-FA group, simple 125I seeds group, and combination group (GNRs@SiO2-FA plus 125I seeds). The apoptosis of HepG2 cells was determined by flow cytometry. The expression of Bax mRNA and Bcl-2 mRNA of HepG2 cells were tested by RT-PCR. The apoptosis-related genes (Bax and Bcl-2) and the tumor proliferation cell nuclear antigen (Ki67) proteins expression on HepG2 cells were examined with immunohistochemistry method. Results The flow cytometry examination showed that the apoptosis rate of HepG2 cells in the simple GNRs@SiO2-FA group and simple 125I seeds group was higher than that in blank control group (P<0.05), and the apoptosis rate of the combination group was significantly higher than that of the simple GNRs@SiO2-FA group and the simple 125I seeds group (P< 0.05). The expression level of Bax mRNA in the combination group was higher than that in the simple GNRs@SiO2-FA group and simple 125I seeds group, while the expression level of Bcl-2 mRNA in the combination group was obviously lower than that in the simple GNRs@SiO2-FA group and simple 125I seeds group. Bax protein was expressed on cytoplasm, Bcl-2 protein was expressed on cytoplasm and cell membrane, while Ki67 protein was expressed on nucleus. All of them presented as brown finely granular precipitations. Statistically significant differences in the amount of Bax, Bcl-2 and Ki67 protein expression existed between each other among the four groups (P< 0.05). The positive expression rate of Bax protein in the combination group was significantly higher than that of the simple GNRs@SiO2-FA group and the simple 125I seeds group, while the positive expression rate of Bcl-2 and Ki67 protein was significantly lower than that of the simple GNRs@SiO2-FA group and the simple 125I seeds group, and the differences were statistically significant (P < 0.05). Conclusion The combination use of GNRs@SiO2-FA and 125I seeds can more effectively induce the apoptosis of HepG2 cells. This effect may be accomplished through increasing the expression of Bax protein and inhibiting the expression of Bcl-2 and Ki67 proteins.
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Objective To synthesize a photoacoustic contrast agent loaded with gold nanorod and liquid perflurocarbon which was used to observe its photoacoustic imaging in vitro,and then investigate the variation of the photoacoustic signal during and after the vaporization.Methods The PLGA nanoparticle (GNP)loaded with gold nanorod(GNR) and liquid perflurocarbon was synthesized via double emulsion technology.The experiments were divided into three groups:1)GNP group:PLGA nanoparticle loaded with gold nanorod and liquid perflurocarbon; 2) GNR group:gold nanorod ; 3) control group:PLGA nanoparticle unloaded with gold nanorod.A pulsed laser system was used to trigger the three samples.The photoacoustic image and time-signal intensity kinetics were acquired by the photoacoustic microscope.The optical microscope was used to observe the image after the vaporization.Results The gold nanoparticle was successfully prepared,the average size of the gold nanoparticle was 504.9 nm.after triggered by the pulsed laser system,the vaporized image of the GNP group could be observed by the optical microscope.The photoacoustic signal was detected in both GNP and GNR groups,and the signal intensity increased along with the concentration of the GNR.However,the photoacoustic signal of PLGA group was not detected.The photoacoustic signal kinetics of GNP group showed a descending trend from high signal amplitude to steadystate.The GNR group photoacoustic signal kinetics only showed a steady-state signal amplitude.Conclusions The PLGA nanoparticle loaded with gold nanorod and liquid perflurocarbon emerged a phase transient which produces a strong photoacoustic signal after triggered by pulsed laser system.This kind of phenomenon leads the nanoparticle to be a better photoacoustic contrast agent and lays a foundation for in vivo research and photothermal therapy in vivo.