Insonation facilitates plasmid DNA transfection into the central nervous system and microbubbles enhance the effect

Manome, Yoshinobu; Nakayama, Naoto; Nakayama, Kiyoshi; Furuhata, Hiroshi

doi:10.1016/j.ultrasmedbio.2005.01.015

Cited by 50 publications

(31 citation statements)

References 48 publications

(55 reference statements)

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“…39 Interestingly, we also found that Optison alone could enhance gene delivery in peritoneal tissues at levels lower than ultrasoundmicrobubble-mediated delivery. These findings are in accord with the observation by Lu et al 37 that microbubbles alone significantly increase the gene transfer in mouse skeletal muscle in vivo even in the absence of ultrasound, but contrast to the observation by Manome et al 36 that no expression of delivered gene Figure 2 Hematoxylin-eosin staining of parietal and visceral peritoneum in rats. Hemorrhage, necrosis or increased accumulation of neutrophils and lymphocytes was not observed in the submesothelial layer of anterior abdominal wall and the interstitium of mesentery in rats receiving transfection.…”

Section: Discussionsupporting

confidence: 89%

“…15,33 Microbubbles collapse by insonation and the gas bodies are removed from the circulation within about 5 min in mice and 15 min in humans. 34,35 Similar to earlier observations that ultrasound increases transfection efficiency in a variety of tissues in vivo including brain, heart and muscle, 12,36,37 we observed increased expression of delivered gene in both parietal and visceral peritoneum following ultrasound exposure. In addition, compared with intraperitoneal gene transfection using polyethylenimine, only very low amount of transgene remained detectable after 72 h, 38 the transgene persists longer in our study signifying the high transfection efficiency by this ultrasound-microbubble-mediated system.…”

Section: Discussionsupporting

confidence: 89%

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Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat

et al. 2007

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Gene transfer into the peritoneal cavity by nonviral methods may provide an effective therapeutic approach for peritoneal diseases. Herein, we investigated the feasibility and the effectiveness of ultrasound-microbubble-mediated delivery of naked plasmid DNA into the peritoneal cavity in rats. Following the intraperitoneal or the intravenous administration of a mixture of plasmid DNA (100 mg) and ultrasound contrast agent microbubbles, an ultrasound transducer was applied on the abdominal wall. The reporter pTRE plasmid encoding Smad7 was used to evaluate transfection efficiency. Smad7 expression was induced by doxycycline in drinking water. We detected less than 10% apoptotic cells and no inflammatory reaction in peritoneal tissues following the ultrasound-microbubble-mediated transfection. More importantly, the insonation significantly improved the transfection efficiency in peritoneal tissues. The transfection efficiency by intraperitoneal delivery route was higher than the intravenous route. The reporter gene, pTRE-Smad7, was readily detected in the parietal peritoneum, mesentery, greater omentum and adipose tissue. The peak of transgene expression occurred 2 days after transfection and the transgene expression diminished in a time-dependent manner thereafter. Overall, the effectiveness and simplicity of the ultrasound-microbubble-mediated system may provide a promising nonviral means for improving gene delivery for treating peritoneal diseases in vivo.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat

et al. 2007

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“…[13][14][15] Three areas have attracted the most attention with respect to US-enhanced drug or nonviral gene delivery: (1) tumor treatment, [16][17][18][19] (2) cardiovascular treatment [20][21][22][23] and (3) skeletal muscle treatment. [24][25][26] UTMD-enhanced gene transfer in vivo or ex vivo has also been explored in the cornea, 27 spinal cord, 28,29 brain tissues, 30,31 kidneys, 32 pancreas, 33 liver, 2 embryonic tissues, 34 intervertebral discs 35 and dental pulp. 36 Although acoustic cavitation is generally associated with sonoporation, in many of these studies the specific mechanism responsible for increasing the gene delivery efficiency is uncertain.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound with microbubbles enhances gene expression of plasmid DNA in the liver via intraportal delivery

et al. 2008

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Current ultrasound (US)-mediated gene delivery methods are inefficient due, in part, to a lack of US optimization. We systematically explored the use of microbubbles (MBs), US parameters and plasmid delivery routes to improve gene transfer into the mouse liver. Co-presentation of plasmid DNA (pDNA), 10% Optison MBs and pulsed 1-MHz US at a peak negative pressure of 4.3 MPa significantly increased luciferase gene expression with pDNA delivered by intrahepatic injection to the left liver lobe. Intraportal injection delivered pDNA and MBs to the whole liver; with insonation, all lobes expressed the transgene, thus increasing total gene expression. Gene expression was also dependent on acoustic pressure over the range of 0-4.3 MPa, with a peak effect at 3 MPa. An average of 85-fold enhancement in gene delivery was achieved. No enhancement was observed below 0.25 MPa. Increasing pulse length while decreasing pulse repetition frequency and exposure time to maintain a constant total energy during exposure did not further improve transfection efficiency, nor did extend the US exposure pre-or postinjection of pDNA. The results indicate that coupled with MBs, US can more efficiently and dose-dependently enhance gene expression from pDNA delivered via portal vein injection by an acoustic mechanism of inertial cavitation.

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“…However, the present study used low-frequency (21 kHz) and low-energy ultrasound, which is associate with easy penetration of the organism, less tissue absorption and reduced tissue injury. Low-frequency ultrasound predominantly induces mechanical and cavitation effects, and the temperature increase through the thermal effect is virtually negligible (36). The results of the present study demonstrated that low-frequency and low-energy ultrasound combined with microbubbles minimally induced the lysis of PC-3 cells.…”

Section: Discussionmentioning

confidence: 48%

Liposome-mediated transfection of wild-type P53 DNA into human prostate cancer cells is improved by low-frequency ultrasound combined with microbubbles

Bai

Zhang

et al. 2016

Oncology Letters

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Abstract. Prostate cancer is a common type of cancer in elderly men. The aim of the present study was to evaluate the effects of ultrasound exposure in combination with SonoVue microbubbles on liposome-mediated transfection of wild-type P53 genes into human prostate cancer cells. PC-3 human prostate cancer cells were exposed to ultrasound; duty cycle was controlled at 20% (2 sec on, 8 sec off) for 5 min with and without SonoVue microbubble echo-contrast agent using a digital sonifier (frequency, 21 kHz; intensity, 46 mW/cm 2 ). The cells were divided into eight groups, as follows: Group A (SonoVue + wild-type P53), group B (ultrasound + wild-type P53), group C (SonoVue + ultrasound + wild-type P53), group D (liposome + wild-type P53), group E (liposome + SonoVue + wild-type P53), group F (liposome + wild-type P53 + ultrasound), group G (liposome + wild-type P53 + ultrasound + SonoVue) and the control group (wild-type P53). Following treatment, a hemocytometer was used to measure cell lysis, reverse transcription-quantitative polymerase chain reaction and western blotting were performed to detect P53 gene transfection efficiency, Cell Counting Kit-8 was employed to reveal cell proliferation and Annexin V/propidium iodide staining was used to determine cell apoptosis. Cell lysis was minimal in each group. Wild-type P53 gene and protein expression were significantly increased in the PC-3 cells in group G compared with the control and all other groups (P<0.01). Cell proliferation was significantly suppressed in group G compared with the control group and all other groups (P<0.01). Cell apoptosis levels in group G were significantly improved compared with the control group and all other groups (P<0.01). Thus, the results of the present study indicate that the use of low-frequency and low-energy ultrasound in combination with SonoVue microbubbles may be a potent physical method for increasing liposome gene delivery efficiency.

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Insonation facilitates plasmid DNA transfection into the central nervous system and microbubbles enhance the effect

Cited by 50 publications

References 48 publications

Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat

Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat

Ultrasound with microbubbles enhances gene expression of plasmid DNA in the liver via intraportal delivery

Liposome-mediated transfection of wild-type P53 DNA into human prostate cancer cells is improved by low-frequency ultrasound combined with microbubbles

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