Thrombolysis effect of a novel targeted microbubble with low-frequency ultrasound in vivo

2008 ◽  
Vol 100 (08) ◽  
pp. 356-361 ◽  
Author(s):  
Bing Wang ◽  
Li Wang ◽  
Xiao-Bo Zhou ◽  
Ya-Min Liu ◽  
Mei Wang ◽  
...  
Keyword(s):  
Low Frequency ◽  
Arterial Occlusion ◽  
Clot Lysis ◽  
In Vivo Model ◽  
Low Frequency Ultrasound ◽  
Targeted Microbubbles ◽  
The Common ◽  
To Receive ◽  
Frequency Ultrasound

SummaryClot-targeted microbubbles (TMB) were developed based on oligopeptide specific to the glycoprotein IIb/IIIa receptor on active platelets. In this study, we aimed to elucidate the thrombolysis effect of this TMB in both intraarterial and intravenous application and compare the clot lysis efficiency of the TMB and untargeted microbubbles(UTMB) in presence of external low frequency ultrasound (LFUS) (800kHz, 2.4w/cm2, pulse-wave). An acute arterial occlusion model was induced in rabbits by blocking the common carotid artery with an autogenous clot. Animals were randomized to five groups to receive the following treatment: 1) intra-arterial TMB and LFUS (IA TMB/LFUS); 2) intravenous TMB and LFUS (IV TMB/LFUS); 3) intravenous untargeted-microbubbles and LFUS (IV UTMB/LFUS);4) LFUS only; 5) intra-arterial normal saline (NS) control. Declotting score and a variation of thrombolysis-in-myocardial-infarction (TIMI) flow scale were applied to assess clot clearance and flow restore according to the angiogram. IA TMB/LFUS treatment produced highest declotting score (3.5 ± 0.53) and success rate (100%).IV TMB/LFUS treatment produced a higher declotting score (1.95 ± 1.12) than LFUS treatment (0.53 ± 0.38) (P=0.026).and higher TIMI (1.94 ± 0.62 vs.0.47 ± 0.44, P=0.020).When administrated intravenously, TMB/LFUS created a higher declotting score (1.95 ± 1.12) than that of UTMB/LFUS (0.61 ± 0.43) (P=0.033).The superiority was observed in TIMI also (1.94 ± 0.62 vs.0.72 ± 0.25, P=0.041).The results demonstrate that either intra-arterial or intravenous TMB is effective in clearing clot in-vivo model. The TMB showed advantage over UTMB in systemic administration.

scholarly journals Low-frequency ultrasound-mediated cytokine transfection enhances T cell recruitment at local and distant tumor sites

2020 ◽  
Vol 117 (23) ◽  
pp. 12674-12685
Author(s):  
Tali Ilovitsh ◽  
Yi Feng ◽  
Josquin Foiret ◽  
Azadeh Kheirolomoom ◽  
Hua Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Low Frequency ◽  
Fold Increase ◽  
T Cell Infiltration ◽  
Low Frequency Ultrasound ◽  
Targeted Microbubbles ◽  
Distant Tumor ◽  
Frequency Ultrasound

Robust cytotoxic T cell infiltration has proven to be difficult to achieve in solid tumors. We set out to develop a flexible protocol to efficiently transfect tumor and stromal cells to produce immune-activating cytokines, and thus enhance T cell infiltration while debulking tumor mass. By combining ultrasound with tumor-targeted microbubbles, membrane pores are created and facilitate a controllable and local transfection. Here, we applied a substantially lower transmission frequency (250 kHz) than applied previously. The resulting microbubble oscillation was significantly enhanced, reaching an effective expansion ratio of 35 for a peak negative pressure of 500 kPa in vitro. Combining low-frequency ultrasound with tumor-targeted microbubbles and a DNA plasmid construct, 20% of tumor cells remained viable, and ∼20% of these remaining cells were transfected with a reporter gene both in vitro and in vivo. The majority of cells transfected in vivo were mucin 1+/CD45−tumor cells. Tumor and stromal cells were then transfected with plasmid DNA encoding IFN-β, producing 150 pg/106cells in vitro, a 150-fold increase compared to no-ultrasound or no-plasmid controls and a 50-fold increase compared to treatment with targeted microbubbles and ultrasound (without IFN-β). This enhancement in secretion exceeds previously reported fourfold to fivefold increases with other in vitro treatments. Combined with intraperitoneal administration of checkpoint inhibition, a single application of IFN-β plasmid transfection reduced tumor growth in vivo and recruited efficacious immune cells at both the local and distant tumor sites.

scholarly journals A Review of the Combination Therapy of Low Frequency Ultrasound with Antibiotics

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Yun Cai ◽  
Jin Wang ◽  
Xu Liu ◽  
Rui Wang ◽  
Lei Xia
Keyword(s):  
Combination Therapy ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Low Frequency ◽  
Bactericidal Effect ◽  
Low Frequency Ultrasound ◽  
Biofilm Bacteria ◽  
Frequency Ultrasound

Single antimicrobial therapy has been unable to resist the global spread of bacterial resistance. Literatures of availablein vitroandin vivostudies were reviewed and the results showed that low frequency ultrasound (LFU) has a promising synergistic bactericidal effect with antibiotics against both planktonic and biofilm bacteria. It also can facilitate the release of antibiotics from medical implants. As a noninvasive and targeted therapy, LFU has great potential in treating bacterial infections. However, more in-depth and detailed studies are still needed before LFU is officially applied as a combination therapy in the field of anti-infective treatment.

Combined Low-Frequency Ultrasound and Streptokinase Intravascular Destruction of Arterial Thrombi In Vivo

2011 ◽  
Vol 37 (10) ◽  
pp. 1644-1652 ◽  
Author(s):  
Igor E. Adzerikho ◽  
Alexander G. Mrochek ◽  
Vladimir T. Minchenya ◽  
Vyacheslav V. Dmitriev ◽  
Anatoly I. Kulak
Keyword(s):  
Low Frequency ◽  
Low Frequency Ultrasound ◽  
Frequency Ultrasound

Low-Frequency Ultrasound in Medicine: An In Vivo Evaluation

2012 ◽  
Vol 61 (6) ◽  
pp. 1658-1663 ◽  
Author(s):  
Antonino S. Fiorillo ◽  
Domenico Grimaldi ◽  
Donatella Paolino ◽  
Salvatore A. Pullano
Keyword(s):  
Low Frequency ◽  
In Vivo Evaluation ◽  
Low Frequency Ultrasound ◽  
Frequency Ultrasound

scholarly journals Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application

2020 ◽  
Vol 245 (14) ◽  
pp. 1200-1212
Author(s):  
Zhiyong Shen ◽  
Jingjing Shao ◽  
Jianquan Zhang ◽  
Weixing Qu
Keyword(s):  
Nude Mice ◽  
Malignant Tumors ◽  
Case Reports ◽  
Low Frequency ◽  
Carcinoma Cells ◽  
Resonance Imaging ◽  
Tumor Tissues ◽  
Low Frequency Ultrasound ◽  
Frequency Ultrasound

Ultrasound and microbubbles can induce apoptosis of tumor cells. However, the effects of ultrasound and microbubbles (USMB) combined with chemotherapy on in vivo tumors have rarely been studied. This research is to evaluate the efficacy of targeted USMB and chemotherapeutic drugs on apoptosis and inhibition of hepatic carcinoma cells in nude mice. We also summarize case reports of its clinical application. It was divided into three parts: First, the subcutaneous hepatic tumors of nude mice were irradiated with ultrasound (20 kHz, 2 W/cm2, 40% duty cycle) and SonoVue microbubbles injected to the tail vein of the mice followed by chemotherapy comprising cisplatin, mitomycin, and 5-fluorouracil. The apoptosis of hepatoma cells was examined by TUNEL staining, and the expression of the Bax and Bcl-2 proteins in the tumor tissues was detected by immunohistochemistry. The microvasculature of the tumor tissues was observed by transmission electron microscope. Second, orthotopic hepatic tumors in nude mice were irradiated by USMB and chemotherapy. The therapeutic effects were evaluated by magnetic resonance imaging. Third, the malignant tumors in three patients were treated with USMB and chemotherapy. Our results showed that microbubbles focused by low-frequency US ruptured microvessel walls, through which more chemotherapy drugs entered into the carcinoma cells, thus enhancing cell apoptosis, increasing Bax protein expression, and decreasing Bcl-2 expression. The survival period of the nude mice in the USMB and chemotherapy group was the longest, compared with the control, USMB, and chemotherapy (χ2=29.37, P < 0.0001). Magnetic resonance imaging examinations revealed the tumor volumes in nude mice decreased after USMB and chemotherapy (t = 3.91, P = 0.0173). In clinical cases, after USMB and chemotherapy, the diameters of tumors decreased and the symptoms of the patients were relieved. Targeted low-frequency ultrasound combined with chemotherapy can promote tumor cell apoptosis, inhibit tumor growth, and relieve clinical symptoms of patients. Impact statement The novelty of this research is that we used ultrasound cavitation to enhance the effects of chemotherapy in the subcutaneous and orthotopic hepatic carcinomas in nude mice. Case reports of the effects of the targeting ultrasound cavitation and chemotherapy on malignant tumors in clinical patients were also examined. We found that low-frequency ultrasound cavitation combined with chemotherapy is effective in the inhibition of tumor growth to some extent.

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