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Objective:To investigate the effect of self-made phase-change nanodroplets IR780/FA-Nds-DTX as molecular targeted ultrasound contrast agents for accurate diagnosis and combined targeted therapy of pancreatic cancer.Methods:Pancreatic cancer cell lines were cultured in vitro and 50 tumor bearing nude mouse models were established. The experimental group (IR780/ FA-NdS-DTX) and four control groups[ normal saline, Nds(FITC), FA-Nds (FITC) and IR-780] were divided to verify dual-mode targeted imaging. The imaging using the IVIS Imaging System verified the high-efficiency targeted detection ability and near-infrared fluorescence imaging of IR780/FA-Nds-DTX for tumors in vivo, phase transformation induced by low-intensity focused ultrasound and further contrast-enhanced ultrasound imaging verified the high-efficiency aggregation of IR780/FA-Nds-DTX in local tumors and accurate evaluation of tumor contour. The therapeutic effect was observed in the experimental group (IR780/FA-Nds-DTX) and four control groups (FA-Nds-IR780, FA-Nds-DTX, FA-Nds and normal saline). After low-intensity focused ultrasound irradiation for 30s induced microbubble blasting after phase transformation in each group, 808nm photothermal therapy apparatus was used to irradiate tumor area in each group. Two-dimensional ultrasound was used to monitor the changes in tumor volume in each group before and at 3 d, 9 d, 15 d after treatment, and the changes in tumor volume rate and inhibition in each group were statistically analyzed and compared.Results:The amount of IR780/ FA-Nds-DTX locally targeted aggregation was the largest, and the average fluorescence intensity of tumor in the experimental group was significantly higher than that of the control groups: IR780/ FA-Nds-DTX group compared with Nds(FITC) group[(5.12±0.69)×10 7 vs (1.06±0.23)×10 7, P<0.05], IR780/FA-Nds-DTX group compared with FA-Nds (FITC) group [(5.12±0.69)×10 7 vs (2.98±0.34)×10 7, P<0.05], IR780/FA-Nds-DTX group compared with IR-780 group [(5.12±0.69)×10 7 vs (1.54±0.42)×10 7, P<0.05], and there was no fluorescence in tumor area in saline group. Further contrast-enhanced ultrasound imaging after nanodroplet phase transformation could more accurately locate the tumor boundary. After 15 days of photothermal ablation combined with chemotherapy, the growth rate of tumor volume in the IR780/ FA-Nds-DTX treatment group was significantly lower than that in the control groups: IR780/FA-Nds-DTX group compared with FA-Nds-IR780 group[(0.105±0.075) vs (0.405±0.175), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds-DTX group [(0.105±0.075) vs (1.385±0.035), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds group [(0.105±0.075) vs (2.255±0.105), P<0.05], IR780/ FA-Nds-DTX group compared with normal saline group [(0.105±0.075) vs (2.185±0.155), P<0.05]. And the tumor inhibition rate increased significantly: IR780/ FA-Nds-DTX group compared with FA-Nds-IR780 group [(0.93±0.06) vs (0.48±0.17), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds-DTX group [(0.93±0.06) vs (-0.51±0.105), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds group [(0.93±0.06) vs (-1.63±0.115), P<0.05], IR780/ FA-Nds-DTX group compared with normal saline[(0.93±0.06) vs (-1.35±0.245), P<0.05]. Conclusions:The self-made phase-change ultrasound contrast agents IR780/FA-Nds-DTX have good potential clinical value in targeted detection and combined therapy of pancreatic cancer with small lesions or even metastases.
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Objective:To prepare a dual targeting nanobubble both for HER2 target and cancer cell target, and compare the targeting ability with single targeting nanobubble either with HER2 targeting or cancer cell targeting ability in vitro.Methods:Nanobubbles(NBs) were prepared using the modified thin film hydration method and then connected with IR783 directly (NBs-IR783), HER2 antibody Affibody by avidin-biotin method (NBs-Affibody), or both of them (IR783-NBs-Affibody). The size distribution, stability, and biosafety of these contrast agents were observed. Flow cytometry and immunofluorescence were applied to compare the binding rate of these NBs against HER2 positive breast cancer cell in vitro.Results:The average size of NBs-Affibody, NBs-IR783 and IR783-NBs-Affibody was (538.4±95.8)nm, (551.8±114.8)nm, and (482.7±54.3)nm, respectively. The binding rate for HER2 positive cell was 26.6%, 97.6%, 84.5%, while for HER2 negative cell was 5.4%, 99.9% and 99.3%, respectively. The results of dual-labeled flow cytometry showed that the binding rate of IR783-NBs-Affibody mediated by IR783 to HER2 positive breast cancer cells were 79.5% and Affibody mediated HER2 targeting binding rate were 19.4%. However, NBs-IR783 only showed IR783-mediated tumor targeted binding without HER2 targeting ability with binding rate of 2.3%.Conclusions:The prepared IR783-NBs-Affibody has the dual targeting ability for HER2 positive breast cancer cell, which is superior to the single targeting NBs (NBs-Affibody and NBs-IR783). IR783-NBs-Affibody is optimal to meet the imaging requirements of tumor heterogeneity.
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Objective To investigate the value of S-Detect classification in differential diagnosis of breast mass . Methods The data of forty-seven patients with breast mass lesions ( n=61) from our hospital during January to December in 2016 were retrospectively analyzed . Both the man-made BI-RADS classification ( identified by three different specialist physicians with 2 ,5 and 7 years of experience , respectively) and computer S-Detect classification were performed . The sensitivity ,specificity ,accuracy , positive predictive value and negative predictive value of the man-made BI-RADS classification and S-Detect classification of the benign or malignant diagnosis of breast lumps were calculated . The ROC curve was further plotted ,and the area under the curve ( AUC) of each group was compared ,respectively . Results Sixty-one breast mass lesions were confirmed 36 benign lesions and 25 malignant lesions by pathological biopsy . The sensitivity ,specificity and accuracy of man-made BI-RADS classification were as follows:2-year experience physicians 69 .4％ ,72 .0％ and 70 .5％ ;5-year experience physicians:64 .0％ ,92 .0％ and 75 .4％ ;7-year experience physicians:69 .4％ , 92 .0％ and 78 .7％ . The diagnostic sensitivity , specificity , and accuracy of S-Detect classification were 80 .6％ ,96 .0％ and 86 .9％ . The specificity ,accuracy and positive predictive value of S-Detect classification were significantly higher than those of 2-year experience physicians by BI-RADS classification ( P <0 .05) . The area under the ROC curve of each group was 0 .729 ,0 .786 and 0 .801 for 2 , 5 and 7-year experience physicians , respectively , and 0 .917 for S-Detect classification . Conclusions Compared with the man-made BI-RADS classification ,S-Detect classification has advantages in diagnosis of the benign or malignant of breast mass and is helpful to improve the accuracy of diagnosis , especially for junior physicians .
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Objective To research the Annexin V-nanoscale ultrasound contrast agents'preparation, ultrasound imaging and the ability to binding apoptosis cells of tumor in vitro.Methods The nanoscale bubble (Nanobubbles,NBs ) packaged the octaflouropropane (C3 F8 ) gas was prepared by thin film hydration.The Annexin V-Nanobubbles (AVNBs ) solutions was acquired through conjugating the biotinylated-Annexin V to the surface of the NBs by biotin-streptavidin bridging chemistry.The size and zeta potential of AVNBs were measured by NanoPlus-3 zeta/nano particle analyzer.The shift in size distribution of AVNBs bubbles was analyzed for the stability,after it was stored at 4 ℃ for different time. AVNB's shape were measured by scanning electron microscopy.The AVNBs bubble was measured using an ultrasound system for echogenicity in vitro,and SonoVue was for control.Finally,the ability of AVNBs binding with apoptosis cells of tumor in vitro was determine via the fluorescence microscope.Results AVNBs has a size distribution of (640.2±32.1 )nm,and a mean zeta potential of (-23.30 ±5.71 )mV.Its size remained relatively constant and appeared to show less size variation within the 24 h analysis period. AVNBs solutions were visible milky white and slightly suspension liquid with the naked eye.Under scanning electron microscopy,AVNBs were uniform hollow sperical cavitation bubble with small size and larger dispersibility in solution.The AVNBs and SonoVue solution had the same higher grayscale signal intensity by ultrasonic imaging.The AVNBs binded well with apoptosis cells of tumor in vitro,and the rate of binding was (97.55 ± 1 .30 )%.Conclusions The AVNBs particles prepared by method of thin film hydration have a nanoscale size,good stability and echogenicity.It can be targeted binding with the apoptosis cells of tumor in vitro.