Ultrasound-Mediated Gene and Drug Delivery Using a Microbubble-Liposome Particle System

Yoon, Young Il; Kwon, Yong-Su; Cho, Hee Sang; Heo, Sun Hee; Park, Kyeong S.oon; Park, Sang G.yu; Lee, Soo Hong; Hwang, Sung Il; Kim, Young I.l.; Jae, Hwan Jun; Ahn, Gook Jun; Cho, Young Seok; Lee, Hakho; Lee, Hak Jong; Yoon, Tae Jong

doi:10.7150/thno.9945

Cited by 96 publications

(66 citation statements)

References 40 publications

(31 reference statements)

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“…First, USMB can burst blood vessels and improve vascular permeability; drugs could go through the ruptured vessel wall and contact with tumor cells, thus increasing the concentration of the drugs around malignant cells. Second, USMB can increase the permeability of the cell walls by sonoporation (28,35,36), which can facilitate the movement of drugs or genes into cells (3,37), thereby increasing the concentration of the drugs in tumor cells. Third, USMB can induce diverse chemical and biological effects, including promoting cell apoptosis, and inhibiting cell proliferation and the neovasculature (33,38).…”

Section: A B C Discussionmentioning

confidence: 99%

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

et al. 2016

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Abstract. The aim of the present study was to investigate whether low-frequency ultrasound (US)-mediated microvessel disruption combined with docetaxel (DTX) can be used as a novel type of chemoembolization. Mice were assigned to four groups: i) The USMB group, treated with low-frequency US combined with microbubbles (USMB); ii) the DTX group, treated with DTX; iii) the USMB + DTX group, treated with combined therapy; and iv) the control group, which was untreated. Immediately after the first treatment, the average peak intensity (API) on contrast-enhanced US was calculated, and tumors were excised for hematoxylin and eosin (HE) staining. At 2 weeks post-treatment, the tumor volumes and wet weights were calculated, and tumors were excised for immunohistochemistry to calculate apoptotic index (AI), proliferative index (PI) and microvessel density (MVD) values. Immediately after the first treatment, in the DTX and control groups, the tumors demonstrated abundant perfusion enhancement, while in the USMB + DTX and USMB groups, blood perfusion of the tumors was interrupted. Compared with that of the control group, the API was significantly lower in the USMB + DTX USMB groups (all P<0.001). HE staining showed that tumor microvasculature was disrupted into flaky hematomas and severely dilated microvessels in the USMB + DTX and USMB groups. In the DTX and control groups, there was no distinct evidence of the disruption and dilation of blood microvessels. At the end of the treatment, the mean tumor inhibition ratio was 73.33, 46.67 and 33.33% for the USMB + DTX, DTX and USMB groups, respectively. The USMB + DTX group had the highest AI, and the lowest PI and MVD compared with the other groups, although the difference between the USMB + DTX and DTX groups with regard to PI and MVD was not significant (USMB + DTX vs. DTX group, P=0.345 and P=0.059, respectively). In conclusion, as a novel type of chemoembolization, USMB combined with DTX is more effective than USMB or DTX alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis.

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Section: A B C Discussionmentioning

confidence: 99%

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

et al. 2016

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“…In comparison with single drug delivery system, co-delivery of drugs through nanocarriers and convey them to the same cancer cell simultaneously (17,18). All formulation were analyzed in terms of size (nm), Polydispersity (Pd) and zeta potential were measured by photon correlation spectroscopy, as summarized in the fig.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Cytotoxicity Effect on McF-7 Cell Line of Co-Encapsulated Artesunate and Curcumin Liposome

Sharma¹,

Kumar²

2017

Int J Pharm Pharm Sci

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Objective: Cancer drug delivery has focused using novel carrier system due to their high drug loading and release controlled property and minimum side effect. Artesunate (ART) and curcumin (CUR) are proved natural herbal lead chemotherapeutics used as Chinese and Indian food. But due to its low absorption and the poor bioavailability limits its clinical efficacy. The object of the present work was to investigate the cytotoxic vs apoptotic effect of these herbal lead molecules in the co-encapsulated liposome formulation.Methods: ART and CUR liposome were prepared by thin film hydration method. Because of their opposite solubility nature, ART loaded in the aqueous phase at pH 7.4 while CUR is present in the central core through lipophilic interaction. In vitro cytotoxicity action of the free and liposomal formulation was performed by MTT assay.Results: Physiochemical parameters were evaluated and compared to the co-encapsulated formulation of containing both molecules. The mean diameter around 200 nm, low polydispersity index and co-encapsulation efficiency were found to be 90%. Co-encapsulation in nanometer size is beneficial for uptake and photo-stability of a drug. The in vitro cytotoxic effect of the co-encapsulated formulation was shown a better result than individual drug and also gives the clue for apoptosis. IC50 value for ART, CUR and Liposome was found to be 297.61 µg/ml and 60.60 µg/ml respectively. The result explained the co-encapsulation of curcumin with artesunate is show an ameliorative effect for repositioning therapeutic efficacy of the drug. Conclusion:We observed that human breast cancer MCF-7 cells were relatively resistant to ART and sensitive to CUR. Treatment with ART plus CUR had a synergistic cytotoxic, and apoptotic effect was mediated by up regulation of DR4 and DR5 m RNA expression.

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“…New Zealand white rabbits aged 5-6 months, weighing 2.6 ± 0.4 kg (Shanghai Sixth People's Hospital, SCXK: 2012-0007), were recruited, and a model of MI was established using the modified Fujita method as previously described [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. The rabbits were first anesthetized by ear vein injection of 3% pelltobarbitalum natricum (30 mg/kg), and fixed using a surgical stent on supine position without tracheal intubation and mechanical ventilation (the tongue was pulled out to keep airway patency).…”

Section: Methodsmentioning

confidence: 99%

“…Ultrasound (US) microbubble contrast agent was also an effective vector, which has been used in US thrombolysis, gene transfer and drug delivery [14]. When injected into arteries, microbubbles could not only enhance ultrasonic backscatter, but also release inclusions in microbubbles by cavitation with high targeting and specificity [15].…”

Section: Introductionmentioning

confidence: 99%

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

Yang

Tang²,

Tao³

et al. 2016

Cardiology

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Objectives: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). Methods: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. Results: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. Conclusion: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

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Ultrasound-Mediated Gene and Drug Delivery Using a Microbubble-Liposome Particle System

Cited by 96 publications

References 40 publications

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization

In Vitro Cytotoxicity Effect on McF-7 Cell Line of Co-Encapsulated Artesunate and Curcumin Liposome

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

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