RGD peptide-modified phase-change nanoparticles combining with low-intensity focused ultrasound for targeting and imaging experiments of gastric cancer in vivo and vitro / 中华超声影像学杂志

Objective To prepare RGD peptide modified perfluorohexane ( PFH ) polymer nanoparticles RGD-PFH-NPs and investigate its basic characteristics ,targeting ability and combine with low-intensity focused ultrasound ( LIFU ) for ultrasonic imaging in vivo and vitro . Methods Targeted nanoparticles RGD-PFH-NPs were prepared by double emulsifying method and carbodiimide method . Their morphology and distribution were observed . The particle size ,zeta potential and connection probability were measured . The phase-changed properties and the LIFU-induced imaging ability in contrast-enhanced ultrasound mode of RGD-PFH-NPs were investigated in vivo and vitro . The tagetability of nanoparticles to human gastric cancer cell line MGC803 and tumor-bearing nude mouse were observed through targeting group and non-targeting group . Results The prepared sample was milky white suspension liquid . The RGD-PFH-NPs were spherical uniform size ,good dispersion when observed through the optical microscope and transmission electron microscopy . The particle size was ( 259 .3 ± 42 .6) nm and the Zeta potential was ( -17 .6+5 .4) mV . The connection probability of RGD peptide was 89 .13％ . With 70℃ water bath and LIFU stimulation RGD-PFH-NPs can remarkably change phase and show good imaging performance in both conventional ultrasound and contrast-enhanced ultrasound mode in vivo and vitro . The connection probability to MGC803 cells in targeting group ( RGD-PFH-NPs ) and the non-targeting group( PFH-NPs)were 82 .59％ and 2 .96％ . The accumulation of nanoparticles in the RGD-PFH-NPs group in tumor tissues was significantly higher than that in the non-targeted PFH-NPs group( P) . Conclusions The constructed nanoparticles RGD-PFH-NPs ,providing contrast-enhanced ultrasonic imaging and excellent targeting ability to human gastric cancer cells MGC803 and gastric cancer tissue ,is expected to become a new type of gastric cancer targeted ultrasound contrast agent .

RGD peptide‐modified phase‐change nanoparticles combining with low‐intensity focused ultrasound for targeting and imaging experiments of gastric cancer in vivo and vitro / 中华超声影像学杂志

To prepare RGD peptide modified perfluorohexane ( PFH ) polymer nanoparticles RGD‐PFH‐NPs and investigate its basic characteristics ,targeting ability and combine with low‐intensity focused ultrasound ( LIFU ) for ultrasonic imaging in vivo and vitro . Methods Targeted nanoparticles RGD‐PFH‐NPs were prepared by double emulsifying method and carbodiimide method . T heir morphology and distribution were observed . T he particle size ,zeta potential and connection probability were measured . T he phase‐changed properties and the LIFU‐induced imaging ability in contrast‐enhanced ultrasound mode of RGD‐PFH‐NPs were investigated in vivo and vitro . T he tagetability of nanoparticles to human gastric cancer cell line M GC803 and tumor‐bearing nude mouse were observed through targeting group and non‐targeting group . Results T he prepared sample was milky w hite suspension liquid . T he RGD‐PFH‐NPs were spherical uniform size ,good dispersion w hen observed through the optical microscope and transmission electron microscopy . T he particle size was ( 259 .3 ± 42 .6) nm and the Zeta potential was ( －17 .6+5 .4) mV . T he connection probability of RGD peptide was 89 .13% . With 70℃ water bath and LIFU stimulation RGD‐PFH‐NPs can remarkably change phase and show good imaging performance in both conventional ultrasound and contrast‐enhanced ultrasound mode in vivo and vitro . The connection probability to M GC803 cells in targeting group ( RGD‐PFH‐NPs ) and the non‐targeting group( PFH‐NPs) were 82 .59% and 2 .96% . T he accumulation of nanoparticles in the RGD‐PFH‐NPs group in tumor tissues was significantly higher than that in the non‐targeted PFH‐NPs group( P) . Conclusions The constructed nanoparticles RGD‐PFH‐NPs ,providing contrast‐enhanced ultrasonic imaging and excellent targeting ability to human gastric cancer cells M GC803 and gastric cancer tissue ,is expected to become a new type of gastric cancer targeted ultrasound contrast agent .

Effects of hypoxia inducible factor-2α on promoting angiogenesis of residual hepatocellular carcinoma after high-intensity focused ultrasound ablation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic features of angiogenesis in residual tumors after high intensity focused ultrasound (HIFU),and to determine the temporal effect and mechanism of hypoxia inducible factor-2 alpha (HIF-2a) in the angiogenic process of residual tumors.</p><p><b>METHODS</b>Xenograft tumors of HepG2 cells were generated by subcutaneously inoculating athymic BALB/c nu/nu mice with the hepatoma cells.About 30 days after inoculation,all mice (except in the control group) were treated by HIFU and assigned randomly to the following 7 groups according to various time intervals post-treatment:1st,3rd,5th day and 1st,2nd,3rd,4th week when the residual tumor tissues were obtained from the experimental groups.Protein levels of HIF-2a and vascular growth factor A (VEGF-A) were quantified by immunohistochemistry and western blotting,and mRNA levels were measured by (real-time quantitative) qPCR. Microvascular density (MVD) was calculated by counting the CD31-positive vascular endothelial cells identified by means of an immunohistochemical staining method.</p><p><b>RESULTS</b>Compared with results from the control group,the protein and mRNA levels of HIF-2a expression reached the highest level in the experimental mice at the 2nd week (P=0.000 and P < 0.01 respectively),and were decreased thereafter(3rd week and 4th week, P=0.000 and P < 0.05).VEGF-A expression in the residual tumor tissues group that received HIFU was significantly decreased,compared with the control group,at all time points uPto 1 week (all P=0.000 and P < 0.01),but the levels increased compared to controls in the 2nd through 4th week (all P=0.000, P < 0.05). Similar results were obtained for MVD.</p><p><b>CONCLUSION</b>HIFU treatment can inhibit angiogenesis in residual hepatoma tissues in the short-term (1 to 2 weeks post-treatment) in mice with hepatocellular carcinoma,but can promote angiogenesis overtime (2 to 4 weeks post-treatment); the angiogenic process may involve the HIF-2α/VEGFA pathway.</p>

Changes of hypoxia-inducible factor in residual hepatocellular carcinoma following high-intensity focused ultrasound exposure in nude mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the changes in hypoxia-inducible factor (HIF1α, HIF2α) in the residual tumor cells in nude mice bearing hepatocellular carcinoma (HCC) following treatment with high-intensity focused ultrasound (HIFU).</p><p><b>METHODS</b>Thirty nude mice bearing human HCC received treatment with HIFU. At 1, 3, and 5 days and 1 and 2 weeks after the treatment, the mice were examined for pathological changes of the residual tumor with HE staining; SP immunohistochemistry, Western blotting and real-time quantitative PCR were used to detect the protein and mRNA expressions of HIF1α and HIF2α in the tumor.</p><p><b>RESULTS</b>HE staining revealed the presence of residual tumor cells and large necrotic areas after the treatment. Immunohistochemistry showed a gradual increment of HIF1α protein and mRNA expressions after the treatment, reaching the peak level at 3 days (P<0.05) followed by progressive reduction at 5 days and 1 and 2 weeks. HIF2α expressions at either the protein or mRNA levels exhibited no significant changes within 3 days after the treatment (P>0.05) but increased significantly at 5 days and 1 and 2 weeks (P<0.05).</p><p><b>CONCLUSION</b>The changes of HIF1α and HIF2α in the residual tumor after HIFU treatment in nude mice bearing HCC can be associated with tumor cell apoptosis and angiogenesis after the treatment.</p>