RESUMO
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.
RESUMO
Conventional biomedical imaging modalities in wide clinical use, such as ultrasound imaging, X-ray computed tomography, magnetic resonance imaging, and positron emission tomography, can provide morphological, anatomical, and functional information about biological tissues. However, single mode imaging in conventional medicine provides only limited information for definitive diagnoses. Thus, combinational diagnosis using multiple imaging modalities has become increasingly important. Recently, photoacoustic imaging (PAI) has gained significant attention, and several PAI prototypes have been used in clinical trials. At the same time, PAI has been tested in combination with conventional imaging modalities. For all these imaging modalities, various contrast-enhancing agents have been developed for various purposes. In this review article, we will focus on recent progress in developing dual mode contrast agents for PAI in combination with other conventional imaging modalities.