{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:35:41Z","timestamp":1788510941110,"version":"build-2803163510"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:00:00Z","timestamp":1710892800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:00:00Z","timestamp":1710892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100019266","name":"Korea Medical Device Development Fund","doi-asserted-by":"publisher","award":["RS-2020-KD000009"],"award-info":[{"award-number":["RS-2020-KD000009"]}],"id":[{"id":"10.13039\/100019266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol Exp"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>We investigated the tumor suppression effect of an ultrasound-sensitive doxorubicin-loaded liposome-based nanoparticle, IMP301, to enhance the synergistic effect with focused ultrasound (FUS) in an animal model of pancreatic cancer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Thirty nude mice with xenografts of PANC-1 human pancreatic cancer cells were randomly and prospectively allocated to 6 different groups (5 per group) each for Study-1 (dose\u2013response test) and Study-2 (synergistic effect test). Study-1 consisted of control, gemcitabine, Doxil with FUS, and three different doses of IMP301 (2, 4, 6\u00a0mg\/kg) with FUS groups. Study-2 consisted of control, FUS only, gemcitabine, Doxil with FUS, and IMP301 (4\u00a0mg\/kg) with or without FUS groups. Differences in tumor volume and growth rate were evaluated by one-way ANOVA and Student\u2013Newman\u2013Keuls test.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In Study-1, 4\u00a0mg\/kg or greater IMP301 with FUS groups showed lower tumor growth rates of 14\u2009\u00b1\u20094 mm<jats:sup>3<\/jats:sup>\/day (mean\u2009\u00b1\u2009standard deviation) or less, compared to the control, gemcitabine, and Doxil with FUS groups with rates exceeding 28\u00a0\u00b1 5 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.050). The addition of FUS in Study-2 decreased the tumor growth rate in the IMP301-treated groups from 36\u2009\u00b1\u200917 to 9\u2009\u00b1\u20096, which was lower than the control, FUS only, gemcitabine, and Doxil with FUS groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.050).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>IMP301 combined with FUS exhibited higher tumor growth suppression compared to the use of a conventional drug alone or the combination with FUS. The present study showed the potential of IMP301 to enhance the synergistic effect with FUS for the treatment of pancreatic cancer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Relevance statement<\/jats:title>\n                <jats:p>This article aims to evaluate the synergistic effect of FUS and ultrasound-responsive liposomal drug in tumor growth suppression by using xenograft mouse model of pancreatic ductal adenocarcinoma. FUS-induced ultrasound-sensitive drug release may be a potential noninvasive repeatable treatment option for patients with locally advanced or unresectable pancreatic cancer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Key points<\/jats:title>\n                <jats:p>\u2022 Modification of conventional drugs combined with FUS would maximize tumor suppression.<\/jats:p>\n                <jats:p>\u2022 IMP301 with FUS had higher tumor suppression effect compared to conventional chemotherapy.<\/jats:p>\n                <jats:p>\u2022 This image-guided drug delivery would enhance therapeutic effects of systemic chemotherapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s41747-024-00436-2","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T02:00:06Z","timestamp":1710900006000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tumor suppression effect of ultrasound-sensitive nanoparticles with focused ultrasound in a pancreas cancer xenograft model"],"prefix":"10.1186","volume":"8","author":[{"given":"Soojin","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6946-6042","authenticated-orcid":false,"given":"Jae Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Joo","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Deok","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Cheon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonchul","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hak Jong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"436_CR1","doi-asserted-by":"publisher","first-page":"638","DOI":"10.3390\/cancers14030638","volume":"14","author":"PXE Mouratidis","year":"2022","unstructured":"Mouratidis PXE, Haar GT (2022) Latest advances in the use of therapeutic focused ultrasound in the treatment of pancreatic cancer. Cancers 14:638\u2013662. https:\/\/doi.org\/10.3390\/cancers14030638","journal-title":"Cancers"},{"key":"436_CR2","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/S0140-6736(10)62307-0","volume":"378","author":"A Vincent","year":"2011","unstructured":"Vincent A, Herman J, Schulick R, Hruban RH, Goggins M (2011) Pancreatic cancer. Lancet 378:607\u2013620. https:\/\/doi.org\/10.1016\/S0140-6736(10)62307-0","journal-title":"Lancet"},{"key":"436_CR3","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1016\/j.clinthera.2017.08.015","volume":"39","author":"MT Saung","year":"2017","unstructured":"Saung MT, Zheng L (2017) Current standards of chemotherapy for pancreatic cancer. Clin Ther 39:2125\u20132134. https:\/\/doi.org\/10.1016\/j.clinthera.2017.08.015","journal-title":"Clin Ther"},{"key":"436_CR4","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.3390\/pharmaceutics13081135","volume":"13","author":"K Entzian","year":"2021","unstructured":"Entzian K, Aigner A (2021) Drug delivery by ultrasound-responsive nanocarriers for cancer treatment. Pharmaceutics 13:1135\u20131165. https:\/\/doi.org\/10.3390\/pharmaceutics13081135","journal-title":"Pharmaceutics"},{"key":"436_CR5","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1016\/j.ultrasmedbio.2013.06.004","volume":"39","author":"ES Lee","year":"2013","unstructured":"Lee ES, Lee JY, Kim H et al (2013) Pulsed high-intensity focused ultrasound enhances apoptosis of pancreatic cancer xenograft with gemcitabine. Ultrasound Med Biol 39:1991\u20132000. https:\/\/doi.org\/10.1016\/j.ultrasmedbio.2013.06.004","journal-title":"Ultrasound Med Biol"},{"key":"436_CR6","doi-asserted-by":"publisher","first-page":"3710","DOI":"10.1007\/s00330-018-5355-9","volume":"28","author":"E-J Park","year":"2018","unstructured":"Park E-J, Ahn YD, Lee JY (2018) In vivo study of enhanced chemotherapy combined with ultrasound image-guided focused ultrasound (USgFUS) treatment for pancreatic cancer in a xenograft mouse model. Eur Radiol 28:3710\u20133718. https:\/\/doi.org\/10.1007\/s00330-018-5355-9","journal-title":"Eur Radiol"},{"key":"436_CR7","doi-asserted-by":"publisher","first-page":"3046","DOI":"10.1016\/j.ultrasmedbio.2020.07.019","volume":"46","author":"H-J Kang","year":"2020","unstructured":"Kang H-J, Lee JY, Park E-J et al (2020) Synergistic effects of pulsed focused ultrasound and a doxorubicin-loaded microparticle-microbubble complex in a pancreatic cancer xenograft mouse model. Ultrasound Med Biol 46:3046\u20133058. https:\/\/doi.org\/10.1016\/j.ultrasmedbio.2020.07.019","journal-title":"Ultrasound Med Biol"},{"key":"436_CR8","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.3390\/pharmaceutics14071314","volume":"14","author":"Y-S Kim","year":"2022","unstructured":"Kim Y-S, Ko MJ, Moon H et al (2022) Ultrasound-responsive liposomes for targeted drug delivery combined with focused ultrasound. Pharmaceutics 14:1314\u20131328. https:\/\/doi.org\/10.3390\/pharmaceutics14071314","journal-title":"Pharmaceutics"},{"key":"436_CR9","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.3390\/pharmaceutics14071512","volume":"14","author":"H Lee","year":"2022","unstructured":"Lee H, Moon H, Kim H-R (2022) Effects of lipid shape and interactions on the conformation, dynamics, and curvature of ultrasound-responsive liposomes. Pharmaceutics 14:1512\u20131528. https:\/\/doi.org\/10.3390\/pharmaceutics14071512","journal-title":"Pharmaceutics"},{"key":"436_CR10","unstructured":"Moon H, Kim Y-S, Kim HR, Jung EA (2021) Sonosensitive liposome and the method for preparation thereof. Korean Patent KR102336114B1, 8 Dec 2021. https:\/\/patents.google.com\/patent\/KR102336114B1\/en"},{"key":"436_CR11","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/j.ultrasmedbio.2012.03.009","volume":"38","author":"JZ Xia","year":"2012","unstructured":"Xia JZ, Xie FL, Ran LF, Xie XP, Fan YM, Wu F (2012) High-intensity focused ultrasound tumor ablation activates autologous tumor-specific cytotoxic T lymphocytes. Ultrasound Med Biol 38:1363\u20131371. https:\/\/doi.org\/10.1016\/j.ultrasmedbio.2012.03.009","journal-title":"Ultrasound Med Biol"},{"key":"436_CR12","doi-asserted-by":"publisher","first-page":"3611","DOI":"10.7150\/thno.25613","volume":"8","author":"M Chavez","year":"2018","unstructured":"Chavez M, Silvestrini MT, Ingham ES et al (2018) Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation. Theranostics 8:3611\u20133628. https:\/\/doi.org\/10.7150\/thno.25613","journal-title":"Theranostics"},{"key":"436_CR13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s00262-016-1891-9","volume":"66","author":"RJE van den Bijgaart","year":"2017","unstructured":"van den Bijgaart RJE, Eikelenboom DC, Hoogenboom M, F\u00fctterer JJ, den Brok MH, Adema GJ (2017) Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies. Cancer Immunol Immunother 66:247\u2013258. https:\/\/doi.org\/10.1007\/s00262-016-1891-9","journal-title":"Cancer Immunol Immunother"},{"key":"436_CR14","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.4049\/jimmunol.1500541","volume":"196","author":"S Bandyopadhyay","year":"2016","unstructured":"Bandyopadhyay S, Quinn TJ, Scandiuzzi L et al (2016) Low-intensity focused ultrasound induces reversal of tumor-induced T cell tolerance and prevents immune escape. J Immunol 196:1964\u20131976. https:\/\/doi.org\/10.4049\/jimmunol.1500541","journal-title":"J Immunol"},{"key":"436_CR15","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.4049\/jimmunol.1901430","volume":"205","author":"JB Joiner","year":"2020","unstructured":"Joiner JB, Pylayeva-Gupta Y, Dayton PA (2020) Focused ultrasound for immunomodulation of the tumor microenvironment. J Immunol 205:2327\u20132341. https:\/\/doi.org\/10.4049\/jimmunol.1901430","journal-title":"J Immunol"},{"key":"436_CR16","doi-asserted-by":"publisher","first-page":"e159","DOI":"10.1016\/j.lpm.2019.02.025","volume":"48","author":"C Springfeld","year":"2019","unstructured":"Springfeld C, J\u00e4ger D, B\u00fcchler MW et al (2019) Chemotherapy for pancreatic cancer. Presse Med 48:e159\u2013e174. https:\/\/doi.org\/10.1016\/j.lpm.2019.02.025","journal-title":"Presse Med"},{"key":"436_CR17","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41392-021-00659-4","volume":"6","author":"S Wang","year":"2021","unstructured":"Wang S, Zheng Y, Yang F et al (2021) The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives. Signal Transduct Target Ther 6:249\u2013271. https:\/\/doi.org\/10.1038\/s41392-021-00659-4","journal-title":"Signal Transduct Target Ther"}],"container-title":["European Radiology Experimental"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41747-024-00436-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s41747-024-00436-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s41747-024-00436-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T02:01:24Z","timestamp":1710900084000},"score":1,"resource":{"primary":{"URL":"https:\/\/eurradiolexp.springeropen.com\/articles\/10.1186\/s41747-024-00436-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,20]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["436"],"URL":"https:\/\/doi.org\/10.1186\/s41747-024-00436-2","relation":{},"ISSN":["2509-9280"],"issn-type":[{"value":"2509-9280","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,20]]},"assertion":[{"value":"2 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in compliance with the guidelines of ethics for animal studies approved by the Institutional Animal Care and Use Committee in Seoul National University Hospital (IACUC 21\u20130071).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors of this manuscript declare relationships with the following companies: JYL reports the stock option of IMGT Co.; WS and HJL are affiliated with IMGT Co. All the other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39"}}