Ultrasound-responsive nanobubble-mediated gene transfection in the cerebroventricular region by intracerebroventricular administration in mice

Ogawa, Kazuhiro; Fuchigami, Yuki; Hagimori, Masayori; Fumoto, Shintaro; Maruyama, Kazuo; Kawakami, Shigeru

doi:10.1016/j.ejpb.2019.02.003

Cited by 17 publications

(8 citation statements)

References 42 publications

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“…Although the intrapulmonary distribution of gene expression after inhalation is important information for therapeutic applications, it has not yet been elucidated in detail. Our group developed a multicolor deep imaging system using a tissue-clearing method and confocal microscopy in several organs [18][19][20][21]. We herein applied the tissue-clearing method to evaluate the intrapulmonary distribution of transgene expression using a multicolor deep imaging system for the first time.…”

Section: Introductionmentioning

confidence: 99%

Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues

et al. 2020

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The present study investigated a pulmonary delivery system of plasmid DNA (pDNA) and its application to melanoma DNA vaccines. pCMV-Luc, pEGFP-C1, and pZsGreen were used as a model pDNA to evaluate transfection efficacy after inhalation in mice. Naked pDNA and a ternary complex, consisting of pDNA, dendrigraft poly-l-lysine (DGL), and γ-polyglutamic acid (γ-PGA), both showed strong gene expression in the lungs after inhalation. The transgene expression was detected in alveolar macrophage-rich sites by observation using multi-color deep imaging. On the basis of these results, we used pUb-M, which expresses melanoma-related antigens (ubiquitinated murine melanoma gp100 and tyrosinase-related protein 2 (TRP2) peptide epitopes), as DNA vaccine for melanoma. The inhalation of naked pUb-M and its ternary complex significantly inhibited the metastasis of B16-F10 cells, a melanoma cell line, in mice. The levels of the inflammatory cytokines, such as TNF-α, IFN-γ, and IL-6, which enhance Th1 responses, were higher with the pUb-M ternary complex than with naked pUb-M and pEGFP-C1 ternary complex as control. In conclusion, we clarified that the inhalation of naked pDNA as well as its ternary complex are a useful technique for cancer vaccination.

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Section: Introductionmentioning

confidence: 99%

Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues

et al. 2020

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“…In Hs683 human oligodendroglioma model, BBB was tighter than that in GL261 mouse glioblastoma model [25]. Recently, Ogawa et al reported that secretable luciferase was detected in cerebrospinal fluid (CSF) after transfection into the choroid plexus by intracerebroventricular administration of ultrasound-responsive nanobubbles with naked pDNA [26]. So, monitoring transgene expression in the brain by CSF sampling instead of blood sampling might seems feasible.…”

Section: Resultsmentioning

confidence: 99%

Monitoring method for transgene expression in target tissue by blood sampling

Kinoshita

Fumoto

Hori

et al. 2019

Biotechnology Reports

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“…Thus, Seebest-PP may be useful to visualize the spatial distribution of lipidic drug delivery system (DDS) carriers. About evaluation of spatial distribution in DDS fields, we have reported several applications using lipid-preserving tissue clearing methods Clear T2 and ScaleSQ(0) [30][31][32][33][34][35]. In these reports, we have evaluated positional relationship of spatial distribution of gene expression with blood vessels or tissue surface stained with lipidic carbocyanine dyes DiI.…”

Section: Discussionmentioning

confidence: 99%

A pH-Adjustable Tissue Clearing Solution That Preserves Lipid Ultrastructures: Suitable Tissue Clearing Method for DDS Evaluation

et al. 2020

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Visualizing biological events and states to resolve biological questions is challenging. Tissue clearing permits three-dimensional multicolor imaging. Here, we describe a pH-adjustable tissue clearing solution, Seebest (SEE Biological Events and States in Tissues), which preserves lipid ultrastructures at an electron microscopy level. Adoption of polyethylenimine was required for a wide pH range adjustment of the tissue clearing solution. The combination of polyethylenimine and urea had a good tissue clearing ability for multiple tissues within several hours. Blood vessels stained with lipophilic carbocyanine dyes were deeply visible using the solution. Adjusting the pH of the solution was important to maximize the fluorescent intensity and suppress dye leakage during tissue clearing. The spatial distribution of doxorubicin and oxidative stress were observable using the solution. Moreover, spatial distribution of liposomes in the liver was visualized. Hence, the Seebest solution provides pH-adjustable, rapid, sufficient tissue clearing, while preserving lipid ultrastructures, which is suitable for drug delivery system evaluations.

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Ultrasound-responsive nanobubble-mediated gene transfection in the cerebroventricular region by intracerebroventricular administration in mice

Cited by 17 publications

References 42 publications

Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues

Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues

Monitoring method for transgene expression in target tissue by blood sampling

A pH-Adjustable Tissue Clearing Solution That Preserves Lipid Ultrastructures: Suitable Tissue Clearing Method for DDS Evaluation

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