{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:32:15Z","timestamp":1790742735871,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T00:00:00Z","timestamp":1558483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H03535"],"award-info":[{"award-number":["18H03535"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sasakawa Scientific Reserch Grant from the Japan Science Society","award":["2018-6024, 2019-6029"],"award-info":[{"award-number":["2018-6024, 2019-6029"]}]},{"DOI":"10.13039\/501100004017","name":"Japanese Association of Dialysis Physicians","doi-asserted-by":"publisher","award":["2018-13"],"award-info":[{"award-number":["2018-13"]}],"id":[{"id":"10.13039\/501100004017","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>In the present study, we developed a sonoporation system, namely \u201cdirect sonoporation\u201d, for transfecting the peritoneum from a defined surface area to avoid systematic side effects. Here, the transfection characteristics are explained because there is less information about direct sonoporation. Naked pDNA and nanobubbles were administered to diffusion cell attached to the visceral and parietal peritoneum from the liver and peritoneal wall surface, respectively. Then, ultrasound was irradiated. Direct sonoporation showed a higher transfection efficacy at the applied peritoneum site from the liver surface while other sites were not detected. Moreover, transgene expression was observed in the peritoneal mesothelial cells (PMCs) at the applied peritoneum site. No abnormality was observed in the inner part of the liver. Although transgene expression of the visceral peritoneum was tenfold higher than that of the parietal peritoneum, transgene expression was observed in the PMCs on both the applied peritoneum sites. These results suggest that direct sonoporation is a site-specific transfection method of the PMCs on the applied peritoneum site without transgene expression at other sites and show little toxicity in the inner tissues at the applied site via cavitation energy. This information is valuable for the development of an intraperitoneal sonoporation device for treatment of peritoneal diseases such as peritoneal fibrosis.<\/jats:p>","DOI":"10.3390\/pharmaceutics11050244","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T02:22:00Z","timestamp":1558664520000},"page":"244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Application of Direct Sonoporation from a Defined Surface Area of the Peritoneum: Evaluation of Transfection Characteristics in Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Koyo","family":"Nishimura","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Yonezawa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2218-4547","authenticated-orcid":false,"given":"Shintaro","family":"Fumoto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayori","family":"Hagimori","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koyo","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1681\/ASN.2009070694","article-title":"The pathophysiology of the peritoneal membrane","volume":"21","author":"Devuyst","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1681\/ASN.2016010112","article-title":"The current state of peritoneal dialysis","volume":"27","author":"Mehrotra","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1046\/j.1523-1755.2003.08806.x","article-title":"Peritoneal dialysis solution biocompatibility: Definitions and evaluation strategies","volume":"64","author":"Clifford","year":"2003","journal-title":"Kidney Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"ii2","DOI":"10.1093\/ndt\/gfl183","article-title":"Epithelial-to-mesenchymal transition of the mesothelial cell--its role in the response of the peritoneum to dialysis","volume":"21","author":"Selgas","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1046\/j.1523-1755.1999.00381.x","article-title":"Gene therapy for renal anemia in mice with polycystic kidney using an adenovirus vector encoding the human erythropoietin gene","volume":"55","author":"Osada","year":"1999","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1182\/blood.V84.9.2946.2946","article-title":"Stimulation of erythropoiesis by in vivo gene therapy: Physiologic consequences of transfer of the human erythropoietin gene to experimental animals using an adenovirus vector","volume":"84","author":"Setoguchi","year":"1994","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/sj.gt.3301704","article-title":"Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer model","volume":"9","author":"Lee","year":"2002","journal-title":"Gene Ther."},{"key":"ref_8","first-page":"3810","article-title":"Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity","volume":"55","author":"Aoki","year":"1995","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/sj.cgt.7700893","article-title":"Intraperitoneal linear polyethylenimine (L-PEI)-mediated gene delivery to ovarian carcinoma nodes in mice","volume":"13","author":"Louis","year":"2006","journal-title":"Cancer Gene Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2019.02.003","article-title":"Ultrasound-responsive nanobubble-mediated gene transfection in the cerebroventricular region by intracerebroventricular administration in mice","volume":"137","author":"Ogawa","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jconrel.2017.07.015","article-title":"Cationic microbubbles and antibiotic-free miniplasmid for sustained ultrasound\u2013mediated transgene expression in liver","volume":"262","author":"Manta","year":"2017","journal-title":"J. Control Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/j.nano.2014.06.009","article-title":"Kidney-selective gene transfection using anionic bubble lipopolyplexes with renal ultrasound irradiation in mice","volume":"10","author":"Kurosaki","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jconrel.2006.09.008","article-title":"Gene delivery by combination of novel liposomal bubbles with perfluoropropane and ultrasound","volume":"117","author":"Suzuki","year":"2007","journal-title":"J. Control Release"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1016\/j.ultrasmedbio.2013.08.003","article-title":"Membrane perforation and recovery dynamics in microbubble-mediated sonoporation","volume":"39","author":"Hu","year":"2013","journal-title":"Ultrasound Med. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1080\/10717544.2017.1319433","article-title":"Effective intraperitoneal gene transfection system using nanobubbles and ultrasound irradiation","volume":"24","author":"Nishimura","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1038\/sj.gt.3303040","article-title":"Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat","volume":"14","author":"Guo","year":"2007","journal-title":"Gene Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1007\/BF00188531","article-title":"Technique of laparoscopic ultrasound examination of the liver and pancreas","volume":"10","author":"Machi","year":"1996","journal-title":"Surg. Endosc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1046\/j.1469-0705.2000.00172.x","article-title":"Evaluation of real-time imaging using a laparoscopic ultrasound probe during operative endoscopic procedures","volume":"16","author":"Letterie","year":"2000","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1681\/ASN.2008040424","article-title":"HGF and BMP-7 ameliorate high glucose-induced epithelial-to-mesenchymal transition of peritoneal mesothelium","volume":"20","author":"Yu","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_20","first-page":"64","article-title":"Hepatocyte growth factor prevents peritoneal fibrosis in an animal model of encapsulating peritoneal sclerosis","volume":"21","author":"Matsuoka","year":"2008","journal-title":"J. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1248\/bpb.27.1697","article-title":"Liver site-specific gene transfer following the administration of naked plasmid DNA to the liver surface in mice","volume":"27","author":"Hirayama","year":"2004","journal-title":"Biol. Pharm. Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1089\/ees.2018.0203","article-title":"Stability of nanobubbles","volume":"35","author":"Meegoda","year":"2018","journal-title":"Environ. Eng. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/cr.2015.9","article-title":"Cationic nanocarriers induce cell necrosis through impairment of Na(+)\/K(+)-ATPase and cause subsequent inflammatory response","volume":"25","author":"Wei","year":"2015","journal-title":"Cell Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.colsurfb.2018.02.027","article-title":"Perspectives on cavitation enhanced endothelial layer permeability","volume":"168","author":"Peruzzi","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jconrel.2013.08.029","article-title":"Drug delivery to the brain by focused ultrasound induced blood\u2013brain barrier disruption: Quantitative evaluation of enhanced permeability of cerebral vasculature using two-photon microscopy","volume":"172","author":"Nhan","year":"2013","journal-title":"J. Control Release"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"623","DOI":"10.7863\/jum.2012.31.4.623","article-title":"Overview of therapeutic ultrasound applications and safety considerations","volume":"31","author":"Miller","year":"2012","journal-title":"J. Ultrasound Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0006-291X(02)00432-1","article-title":"Liver- and lobe-selective gene transfection following the instillation of plasmid DNA to the liver surface in mice","volume":"294","author":"Kawakami","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1538\/expanim.60.481","article-title":"Effect of three types of mixed anesthetic agents alternate to ketamine in mice","volume":"60","author":"Kawai","year":"2011","journal-title":"Exp. Anim."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7813","DOI":"10.1016\/j.biomaterials.2010.06.058","article-title":"Development of an ultrasound-responsive and mannose-modified gene carrier for DNA vaccine therapy","volume":"31","author":"Un","year":"2010","journal-title":"Biomaterials"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fumoto, S., Nishimura, K., Nishida, K., and Kawakami, S. (2016). Three-dimensional imaging of the intracellular fate of plasmid DNA and transgene expression: ZsGreen1 and tissue clearing method CUBIC are an optimal combination for multicolor deep imaging in murine tissues. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148233"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/nn.4107","article-title":"ScaleS: An optical clearing palette for biological imaging","volume":"18","author":"Hama","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.cell.2014.10.034","article-title":"Whole-body imaging with single-cell resolution by tissue decolorization","volume":"159","author":"Tainaka","year":"2014","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1248\/bpb.b13-00730","article-title":"Novel diagnostic method of peritoneal injury using dual macromolecular markers","volume":"37","author":"Hirata","year":"2014","journal-title":"Biol. Pharm. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/sj.gt.3300947","article-title":"Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA","volume":"6","author":"Liu","year":"1999","journal-title":"Gene Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ijpharm.2015.03.073","article-title":"Development of fluorous lipid-based nanobubbles for efficiently containing perfluoropropane","volume":"487","author":"Oda","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1038\/gt.2011.34","article-title":"Explorations of high-intensity therapeutic ultrasound and microbubble-mediated gene delivery in mouse liver","volume":"18","author":"Song","year":"2011","journal-title":"Gene Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jconrel.2010.04.010","article-title":"The correlation between acoustic cavitation and sonoporation involved in ultrasound-mediated DNA transfection with Polyethylenimine (PEI) in vitro","volume":"145","author":"Qiu","year":"2010","journal-title":"J. Control Release"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1099\/jmm.0.46143-0","article-title":"A quantitative and highly sensitive luciferase-based assay for bacterial toxins that inhibit protein synthesis","volume":"54","author":"Zhao","year":"2005","journal-title":"J. Med. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1083\/jcb.74.1.98","article-title":"Organization of cell junctions in the peritoneal mesothelium","volume":"74","author":"Simionescu","year":"1977","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Shimizu, K., Kawakami, S., Hayashi, K., Kinoshita, H., Kuwahara, K., Nakao, K., Hashida, M., and Konishi, S. (2012). In vivo site-specific transfection of naked plasmid DNA and siRNAs in mice by using a tissue suction device. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041319"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3109\/1061186X.2015.1087526","article-title":"Optimization of renal transfection using a renal suction-mediated transfection method in mice","volume":"24","author":"Taniguchi","year":"2016","journal-title":"J. Drug Target"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/5\/244\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:23Z","timestamp":1760187263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/5\/244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,22]]},"references-count":41,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["pharmaceutics11050244"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics11050244","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,22]]}}}