共查询到20条相似文献,搜索用时 11 毫秒
1.
Charles F. Caskey 《Molecular imaging and biology》2017,19(3):336-340
Ultrasound is a rapidly advancing field with many emerging diagnostic and therapeutic applications. For diagnostics, new vascular targets are routinely identified and mature technologies are being translated to humans, while other recent innovations may bring about the creation of acoustic reporter genes and micron-scale resolution with ultrasound. As a cancer therapy, ultrasound is being explored as an adjuvant to immune therapies and to deliver acoustically or thermally active drugs to tumor regions. Ultrasound-enhanced delivery across the blood brain barrier (BBB) could potentially be very impactful for brain cancers and neurodegenerative diseases where the BBB often impedes the delivery of therapeutic molecules. In this minireview, we provide an overview of these topics in the field of ultrasound that are especially relevant to the interests of World Molecular Imaging Society. 相似文献
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Lynda J.M. Juffermans Bernadet D.M. Meijering Robert H. Henning Leo E. Deelman 《Ultrasound in medicine & biology》2014
Ultrasound and microbubble-targeted delivery (UMTD) is a promising non-viral technique for genetic-based therapy. We found that UMTD of small interfering RNA (siRNA) is more effective than delivery of plasmid DNA (pDNA). UMTD (1 MHz, 0.22 MPa) of fluorescently labeled siRNA resulted in 97.9 ± 1.5% transfected cells, with siRNA localized homogenously in the cytoplasm directly after ultrasound exposure. UMTD of fluorescently labeled pDNA resulted in only 43.0 ± 4.2% transfected cells, with localization mainly in vesicular structures, co-localizing with endocytosis markers clathrin and caveolin. Delivery of siRNA against GAPDH (glyceraldehyde-3-phosphate dehydrogenase) effectively decreased protein levels to 24.3 ± 7.9% of non-treated controls (p < 0.01). In contrast, 24 h after delivery of pDNA encoding GAPDH, no increase in protein levels was detected. Transfection efficiency, verified with red fluorescently labeled pDNA encoding enhanced green fluorescent protein, revealed that of the transfected cells, only 2.0 ± 0.7% expressed the transgene. In conclusion, the difference in localization between siRNA and pDNA after UMTD is an important determinant of the effectiveness of these genetic-based technologies. 相似文献
3.
Tomoki Ouchi Ariunbuyan Sukhbaatar Sachiko Horie Maya Sakamoto Kiyoto Shiga Shiro Mori Tetsuya Kodama 《Ultrasound in medicine & biology》2018,44(8):1818-1827
Conventional treatment of lymph node metastasis involves dissection of the tumor and regional lymph nodes, but this may cause activation of latent metastatic tumor cells. However, there are few reports on animal models regarding the activation of latent metastatic tumor cells and effective methods of treating activated tumor cells. Here, we report the use of a superselective drug delivery system in a mouse model of lung metastasis in which activated tumor cells are treated with doxorubicin-encapsulated liposomes (DOX-LP) and ultrasound. The axillary lymph node was injected with DOX-LP and exposed to ultrasound so that the released DOX would be delivered from the axillary lymph node to the metastatic lung via the subclavian vein, heart and pulmonary artery. The size of the DOX-LP was optimized to a diameter of 460?nm using indocyanine green-encapsulated liposomes, and the ultrasound intensity was 0.5 W/cm2. We found that compared with DOX or DOX-LP alone, the superselective drug delivery system was effective in the treatment of metastasis in both the lung and axillary lymph node. We anticipate that this superselective drug delivery system will be a starting point for the development of new techniques for treating lung metastasis in the clinical setting. Furthermore, the superselective drug delivery system may be used to screen novel drugs for the treatment of lung cancer and investigate the mechanisms of tumor cell activation after resection of a primary tumor or lymph nodes. 相似文献
4.
Paul Christopher Lyon Christophoros Mannaris Michael Gray Robert Carlisle Fergus V. Gleeson David Cranston Feng Wu Constantin C. Coussios 《Ultrasound in medicine & biology》2021,47(4):982-997
Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5–15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm3). We describe successful clinical translation in a first-in-human clinical trial of targeted drug delivery of LTSLs (TARDOX: a phase I study to investigate drug release from thermosensitive liposomes in liver tumours), in which targeted tumour hyperthermia resulted in localised chemo-ablation. The heating strategy is potentially applicable to other indications and ultrasound-guided FUS devices. 相似文献
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高分辨力超声评价高胰岛素血症患者内皮功能的研究 总被引:4,自引:0,他引:4
目的 探讨高分辨力超声评价高胰岛素血症肱动脉血管内皮功能的临床应用及其意义。方法 应用放免法测量患者血浆胰岛素 (INS)水平并据此将原发性高血压 (EH)患者分为高胰岛素血症 (HI)组 17例以及非高胰岛素血症 (NHI)组 30例 ,正常对照组 2 0例。应用 Celermajer的方法 [1 ] ,通过超声检测反应性充血后及舌下含服 0 .5 mg硝酸甘油后肱动脉内径变化来评估血管内皮功能。结果 与对照组相比 ,原发性高血压组内皮依赖性舒张功能明显受损 (P<0 .0 5 ) ,HI组较 NHI组内皮依赖性舒张功能受损更为明显 (P<0 .0 5 )。而 3组内皮非依赖性舒张功能无明显差异 (P>0 .0 5 )。结论 应用高分辨力超声能够准确、简便、有效地评价动脉血管内皮功能。高胰岛素血症对 EH患者内皮细胞功能的紊乱有一定的影响。 相似文献
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Microbubble-Assisted Ultrasound for Imaging and Therapy of Melanoma Skin Cancer: A Systematic Review
《Ultrasound in medicine & biology》2022,48(11):2174-2198
Recent technological developments in ultrasound (US) imaging and ultrasound contrast agents (UCAs) have improved diagnostic confidence in echography. In the clinical management of melanoma, contrast-enhanced ultrasound (CEUS) imaging complements conventional US imaging (i.e., high-resolution US and Doppler imaging) for clinical examination and therapeutic follow-up. These developments have set into motion the combined use of ultrasound and UCAs as a new modality for drug delivery. This modality, called sonoporation, has emerged as a non-invasive, targeted and safe method for the delivery of therapeutic drugs into melanoma. This review focuses on the results and prospects of using US and UCAs as dual modalities for CEUS imaging and melanoma treatment. 相似文献
9.
Cheng-Huang Su Chiung-Yin Chang Hsueh-Hsiao Wang Yih-Jer Wu Thierry Bettinger Cheng-Ho Tsai Hung-I Yeh 《Ultrasound in medicine & biology》2010
Ultrasound, in combination with microbubbles, serves as a feasible nonviral method in vascular gene delivery. However, the effects of ultrasonic microbubble transfection (UMT) on vascular endothelial cells remained unclear. We therefore investigated whether UMT itself causes phenotypic changes of the human aortic endothelial cells (HAEC) in vitro. HAEC were cultured with solution containing luciferase reporter gene and microbubbles followed by exposure to ultrasound of selected parameters. Thereafter, the proliferation and migration activities of HAEC were investigated. Real-time RT-PCR and/or western blotting were performed to assess expression profile of HAEC, including growth-related factors (vascular endothelial growth factor, fins-like tyrosine kinase-1 [Flt-1] and kinase insert domain-containing receptor [KDR]), coagulatory factor (von Willebrand factor), vasodilatory enzyme (endothelial nitric oxide synthase), gap junctional protein connexin43 and adhesion molecules (P-selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1). The results showed that in conditions where UMT lead to expression of luciferase, proliferation capacity is enhanced (p < 0.001), partly attributable to the effect of ultrasound (p < 0.05), after excluding the effect of contact inhibition. In addition, the expression of KDR and Flt-1 were found increased at either the mRNA level, protein level, or both (p < 0.05). Other markers did not have significant changes (all p > 0.2). Similarly, the migration capacity was minimally changed (p > 0.3). In conclusion, UMT causes phenotypic changes of HAEC by enhancing proliferation and upregulating KDR and Flt-1, while possesses no obvious adverse effect on viable transfected cells. Further investigation is required to clarify the impact of these changes by UMT in vivo. (E-mail: hiyeh@ms1.mmh.org.tw) 相似文献
10.
Lynda J.M. Juffermans Annemieke van Dijk Cees A.M. Jongenelen Benjamin Drukarch Arie Reijerkerk Helga E. de Vries Otto Kamp René J.P. Musters 《Ultrasound in medicine & biology》2009
Recent developments in the field of ultrasound (US) contrast agents have demonstrated that these encapsulated microbubbles can not only be used for diagnostic imaging but may also be employed as therapeutic carriers for localized, targeted drug or gene delivery. The exact mechanisms behind increased uptake of therapeutic compounds by US-exposed microbubbles are still not fully understood. Therefore, we studied the effects of stably oscillating SonoVue microbubbles on relevant parameters of cellular and intercellular permeability, i.e., reactive oxygen species (ROS) homeostasis, calcium permeability, F-actin cytoskeleton, monolayer integrity and cell viability using live-cell fluorescence microscopy. US was applied at 1-MHz, 0.1 MPa peak-negative pressure, 0.2% duty cycle and 20 Hz pulse repetition frequency to primary endothelial cells. We demonstrated increased membrane permeability for calcium ions, with an important role for H2O2. Catalase, an extracellular H2O2 scavenger, significantly blocked the influx of calcium ions. Further changes in ROS homeostasis involved an increase in intracellular H2O2 levels, protein nitrosylation and a decrease in total endogenous glutathione levels. In addition, an increase in the number of F-actin stress fibers and F-actin cytoskeletal rearrangement were observed. Furthermore, US-exposed microbubbles significantly affected endothelial monolayer integrity, but importantly, disrupted cell-cell interactions were restored within 30 min. Finally, cell viability was not affected. In conclusion, these data provide more insight in the interactions between US, microbubbles and endothelial cells, which is important for understanding the mechanisms behind US and microbubble-enhanced uptake of drugs or genes. (E-mail: ljm.juffermans@vumc.nl) 相似文献
11.
Daniela Begolo Esteban Erben Christine Clayton 《Antimicrobial agents and chemotherapy》2014,58(10):6260-6264
Elucidation of molecular targets is very important for lead optimization during the drug development process. We describe a direct method to find targets of antitrypanosomal compounds against Trypanosoma brucei using a trypanosome overexpression library. As proof of concept, we treated the library with difluoromethylornithine and DDD85646 and identified their respective targets, ornithine decarboxylase and N-myristoyltransferase. The overexpression library could be a useful tool to study the modes of action of novel antitrypanosomal drug candidates. 相似文献
12.
Cheng-Huang Su Yih-Jer Wu Chiung-Yin Chang Ting-Yi Tien Ssu-Wei Tseng Chung-Hsien Tsai Thierry Bettinger Cheng-Ho Tsai Hung-I. Yeh 《Ultrasound in medicine & biology》2013
We investigated the feasibility of exogenous gene expression in endothelial progenitor cells (EPCs) through the use of ultrasonic microbubble transfection (UMT). EPCs originating from porcine peripheral blood were cultured in a medium containing constructed vascular endothelial growth factor (VEGF) pDNA followed by UMT. Simultaneously, comprehensive functional evaluations were conducted to investigate the effects of UMT of the VEGF gene on the EPCs. The results showed that UMT yielded significant VEGF protein expression. VEGF-containing supernatant originating from EPCs post UMT led to significantly enhanced activities of proliferation by more than 20% and migration by approximately 30% in human aortic endothelial cells. The duration of additional secretion of VEGF protein attributable to the exogenous VEGF gene in the EPCs post UMT lasted more than 96 hours. In conclusion, UMT successfully delivers the VEGF gene into porcine EPCs, and VEGF-containing supernatant derived from EPCs post UMT enhances the proliferation and migration of human aortic endothelial cells. 相似文献
13.
《Ultrasound in medicine & biology》2015,41(10):2740-2754
Ultrasound-mediated drug delivery is a field of research with promising results, although the exact mechanisms underlying intracellular delivery of therapeutic compounds remain to be elucidated. Many studies use drug carriers and cavitation to enhance drug uptake into tumor cells. However, cavitation could induce cell lysis and remain difficult to control and predict in vivo. In this study, low-intensity ultrasound was delivered using two transducers working at 2.9 and 1.3 MHz. The maximal peak negative pressure was 0.29 MPa to avoid cavitation. Low-intensity ultrasound induced clathrin-mediated endocytosis and forced the penetration of a bisphosphonate (zoledronic acid) into MCF-7 human breast cancer cells potentially as a result of mechanical stresses. When sonication parameters were adjusted to create mild hyperthermia in addition to the mechanical stress, further significant accumulation of ZOL was observed. These results provide better insight into the role of acoustic parameters in drug uptake. 相似文献
14.
靶向性声学造影剂与血管内皮细胞相互作用的实验研究 总被引:2,自引:0,他引:2
目的 制备携抗人VCAM-1单克隆抗体的白蛋白声学造影剂,观察其与损伤血管内皮细胞的相互作用,探讨评价血管内皮功能的新方法。
方法 采用交联法将抗人VCAM-1单克隆抗体共价偶联到自制氟碳气体为核心的白蛋白微气泡表面,制备靶向性声学微气泡;倒置显微镜下分别观察普通白蛋白微气泡、靶向性微气泡与正常内皮细胞、损伤内皮细胞的结合作用,高倍视野下计数内皮细胞及黏附的微气泡的数目,通过计算微气泡与内皮细胞的比值对两者之间的结合作用进行定量分析。
结果 无论是正常内皮细胞,或损伤内皮细胞,仅见少量的对照组微气泡的黏附作用;而镜下可见大量携VCAM-1单抗的白蛋白微气泡黏附在损伤内皮细胞表面,黏附数目显著高于黏附于正常内皮细胞表面的数目。
结论 携VCAM-1单抗的靶向性声学造影剂能够特异性结合在损伤内皮细胞表面,开拓了超声成像技术检测血管内皮损伤、评价血管内皮功能新的研究领域。 相似文献
15.
Kevin A. Snook Robert Van Ess Jacob R. Werner Ryan S. Clement Olga M. Ocon-Grove Jeffery W. Dodds Kevin J. Ryan Edward P. Acosta John J. Zurlo Maureen L. Mulvihill 《Ultrasound in medicine & biology》2019,45(2):513-525
Ultrasound-mediated transdermal delivery is a promising parenteral administration method for large-molecule or unstable medications. This study evaluated skin health and systemic delivery when administering enfuvirtide, an injectable anti-retroviral medication, over a 1-mo period in a porcine model using a low-frequency cymbal transducer. Three groups received twice-daily treatments: (i) enfuvirtide injection control (n?=?12); (ii) saline ultrasound control (n?=?6); and (iii) enfuvirtide ultrasound treatment (n?=?13). Ultrasound parameters were as follows: 30-min exposure, 90 mW/cm², 24–26 kHz and 15% duty cycle. No statistical difference in trans-epidermal water loss, a measure of skin health and function, was seen between ultrasound-treated and control skin sites for either saline (p?=?0.50) or enfuvirtide (p?=?0.29) groups. Average trough plasma concentrations of enfuvirtide were 0.6 ± 0.2 and 2.8 ± 0.8 μg/mL for ultrasound and injection, respectively. Tolerability and efficacy results indicate that chronic, low-frequency ultrasound exposure can be a practical means for transdermal delivery of medications such as enfuvirtide. 相似文献
16.
Marc Derieppe Anna Yudina Matthieu Lepetit-Coiffé Baudouin Denis de Senneville Clemens Bos Chrit Moonen 《Molecular imaging and biology》2013,15(1):3-11
Purpose
Transport across the plasma membrane is a critical step of drug delivery for weakly permeable compounds with intracellular mode of action. The purpose of this study is to demonstrate real-time monitoring of ultrasound (US)-mediated cell-impermeable model drug uptake with fibered confocal fluorescence microscopy (FCFM).Procedures
An in vitro setup was designed to combine a mono-element US transducer, a cell chamber with a monolayer of tumor cells together with SonoVue microbubbles, and a FCFM system. The cell-impermeable intercalating dye, SYTOX Green, was used to monitor US-mediated uptake.Results
The majority of the cell population showed fluorescence signal enhancement 10 s after US onset. The mean rate constant k of signal enhancement was calculated to be 0.23?±?0.04 min?1.Conclusions
Feasibility of real-time monitoring of US-mediated intracellular delivery by FCFM has been demonstrated. The method allowed quantitative assessment of model drug uptake, holding great promise for further local drug delivery studies. 相似文献18.
Joseph P. Kilroy Alexander L. Klibanov Brian R. Wamhoff Douglas K. Bowles John A. Hossack 《Ultrasound in medicine & biology》2014
An intravascular ultrasound (IVUS) and microbubble drug delivery system was evaluated in both ex vivo and in vivo swine vessel models. Microbubbles with the fluorophore DiI embedded in the shell as a model drug were infused into ex vivo swine arteries at a physiologic flow rate (105 mL/min) while a 5-MHz IVUS transducer applied ultrasound. Ultrasound pulse sequences consisted of acoustic radiation force pulses to displace DiI-loaded microbubbles from the vessel lumen to the wall, followed by higher-intensity delivery pulses to release DiI into the vessel wall. Insonation with both the acoustic radiation force pulse and the delivery pulse increased DiI deposition 10-fold compared with deposition with the delivery pulse alone. Localized delivery of DiI was then demonstrated in an in vivo swine model. The theoretical transducer beam width predicted the measured angular extent of delivery to within 11%. These results indicate that low-frequency IVUS catheters are a viable method for achieving localized drug delivery with microbubbles. 相似文献
19.
I-Chi Lee Tsu-Lin Lo Tai-Horng Young Yi-Chen Li Nelson G. Chen Chung-Hsuan Chen Ying-Chih Chang 《Ultrasound in medicine & biology》2014
Herein, we report the evaluation of apoptosis, cell differentiation, neurite outgrowth and differentiation of neural stem/progenitor cells (NSPCs) in response to low-intensity ultrasound (LIUS) exposure. NSPCs were cultured under different conditions, with and without LIUS exposure, to evaluate the single and complex effects of LIUS. A lactic dehydrogenase assay revealed that the cell viability of NSPCs was maintained with LIUS exposure at an intensity range from 100 to 500 mW/cm2. Additionally, in comparison with no LIUS exposure, the cell survival rate was improved with the combination of medium supplemented with nerve growth factor and LIUS exposure. Our results indicate that LIUS exposure promoted NSPC attachment and differentiation on a glass substrate. Neurite outgrowth assays revealed the generation of longer, thicker neurites after LIUS exposure. Furthermore, LIUS stimulation substantially increased the percentage of differentiating neural cells in NSPCs treated with nerve growth factor in comparison with the unstimulated group. The high percentage of differentiated neural cells indicated that LIUS induced neuronal networks denser than those observed in the unstimulated groups. Furthermore, the release of nitric oxide, an important small-molecule neurotransmitter, was significantly upregulated after LIUS exposure. It is therefore reasonable to suggest that LIUS promotes the differentiation of NSPCs into neural cells, induces neurite outgrowth and regulates nitric oxide production; thus, LIUS may be a potential candidate for NSPC induction and neural cell therapy. 相似文献
20.
超声评价高脂血症患者肱动脉内皮功能 总被引:4,自引:0,他引:4
目的 利用高分辨率超声评价高脂血症 (hyperlipidemia,HL P)患者肱动脉内皮依赖性舒张功能的变化。方法 将 80名研究对象分为 4组。 组 2 0人为正常对照组 , - 组分别为高胆固醇血症组、高甘油三酯血症组和混合性高脂血症组。应用高分辨率超声分别观察记录静息状态下、反应性充血和舌下含服硝酸甘油后的肱动脉内径变化。结果 与正常对照组相比 ,高脂血症患者肱动脉血管内皮依赖性舒张功能明显降低、尤以混合性高脂血症组为甚 (11.3± 3.1) %比 (5 .7± 3.2 ) % ,(5 .4± 3.0 ) %比 (3.8± 2 .4 ) % ,P均 <0 .0 5 )。结论 HL P患者血管内皮依赖性舒张功能较正常人明显受损 ,高分辨率超声能准确可靠地检测血管内皮依赖性舒张功能。 相似文献