{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:38:08Z","timestamp":1790959088729,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T00:00:00Z","timestamp":1518134400000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T00:00:00Z","timestamp":1486598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMR\u20101006601"],"award-info":[{"award-number":["DMR\u20101006601"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["WIREs Nanomed Nanobiotechnol"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:p>Nanoparticle (<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>)\u2010based drug\u2010delivery systems are frequently employed to improve the intravenous administration of chemotherapy; however, few reports explore their application as an intraperitoneal therapy. We developed a<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>\u2010responsive expansile nanoparticle (<jats:styled-content style=\"fixed-case\">eNP<\/jats:styled-content>) specifically designed to leverage the intraperitoneal route of administration to treat intraperitoneal malignancies, such as mesothelioma, ovarian, and pancreatic carcinomatoses. This review describes the design, evaluation, and evolution of the<jats:styled-content style=\"fixed-case\">eNP<\/jats:styled-content>technology and, specifically, a<jats:italic>Materials\u2010Based Targeting<\/jats:italic>paradigm that is unique among the many active\u2010 and passive\u2010targeting strategies currently employed by<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>\u2010delivery systems.<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>\u2010responsive<jats:styled-content style=\"fixed-case\">eNP<\/jats:styled-content>swelling is responsible for the extended residence at the target tumor site as well as the subsequent improvement in tumoral drug delivery and efficacy observed with paclitaxel\u2010loaded<jats:styled-content style=\"fixed-case\">eNPs<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">PTX\u2010eNPs<\/jats:styled-content>) compared to the standard clinical formulation of paclitaxel, Taxol\u00ae. Superior<jats:styled-content style=\"fixed-case\">PTX\u2010eNP<\/jats:styled-content>efficacy is demonstrated in two different orthotopic models of peritoneal cancer\u2014mesothelioma and ovarian cancer; in a third model\u2014of pancreatic cancer\u2014<jats:styled-content style=\"fixed-case\">PTX\u2010eNPs<\/jats:styled-content>demonstrated comparable efficacy to Taxol with reduced toxicity. Furthermore, the unique structural and responsive characteristics of<jats:styled-content style=\"fixed-case\">eNPs<\/jats:styled-content>enable them to be used in three additional treatment paradigms, including: treatment of lymphatic metastases in breast cancer; use as a highly fluorescent probe to visually guide the resection of peritoneal implants; and, in a two\u2010step delivery paradigm for concentrating separately administered<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>and drug at a target site. This case study serves as an important example of using the targeted disease\u2010state's pathophysiology to inform the<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>design as well as the method of use of the delivery system.<jats:italic>WIREs Nanomed Nanobiotechnol<\/jats:italic>2017, 9:e1451. doi: 10.1002\/wnan.1451<\/jats:p><jats:p>This article is categorized under:<jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>Diagnostic Tools &gt; Diagnostic Nanodevices<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Therapeutic Approaches and Drug Discovery &gt; Nanomedicine for Oncologic Disease<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p>","DOI":"10.1002\/wnan.1451","type":"journal-article","created":{"date-parts":[[2017,2,10]],"date-time":"2017-02-10T01:52:40Z","timestamp":1486691560000},"source":"Crossref","is-referenced-by-count":43,"title":["Nanoparticle drug\u2010delivery systems for peritoneal cancers: a case study of the design, characterization and development of the expansile nanoparticle"],"prefix":"10.1002","volume":"9","author":[{"given":"Aaron H.","family":"Colby","sequence":"first","affiliation":[{"name":"Departments of Biomedical Engineering and Chemistry Boston University Boston MA USA"},{"name":"Division of Thoracic Surgery, Department of Surgery Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas H.","family":"Oberlies","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro Greensboro NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric J.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Mycosynthetix, Inc. Hillsborough NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L.M.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Medicine and Whitaker Cardiovascular Institute Boston University School of Medicine Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolonda L.","family":"Colson","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery, Department of Surgery Brigham and Women's Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Grinstaff","sequence":"additional","affiliation":[{"name":"Departments of Biomedical Engineering, Chemistry, and Medicine Boston University Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,9]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.10.100"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.suronc.2010.09.002"},{"key":"e_1_2_16_4_1","first-page":"4071","article-title":"A preliminary study of single intraperitoneal administration of paclitaxel followed by sequential systemic chemotherapy with S\u20101 plus paclitaxel for advanced gastric cancer with peritoneal metastasis","volume":"32","author":"Imano M","year":"2012","journal-title":"Anticancer Res"},{"key":"e_1_2_16_5_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0090-9556(25)06648-6","article-title":"Plasma and tissue disposition of paclitaxel (taxol) after intraperitoneal administration in mice","volume":"23","author":"Innocenti F","year":"1995","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v2.i2.109"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.9898"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/506571"},{"key":"e_1_2_16_9_1","volume-title":"NCT02850874 HIPEC as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma","author":"Vrochides D","year":"2016"},{"key":"e_1_2_16_10_1","unstructured":"Open\u2010label Pilot Phase I\/II Study on Hyperthermic Intraperitoneal Chemotherapy (HIPEC) After Macroscopically Complete Resection (R0\/R1) of Adenocarcinomas of the Pancreas (PanHIPEC). T\u00fcbingen: University Hospital Tuebingen; 2016."},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2005.03.002"},{"key":"e_1_2_16_12_1","unstructured":"Mesothelioma Cancer Trends. Available at:https:\/\/www.asbestos.com\/mesothelioma\/mesothelioma\u2010trends\/. (Accessed September 21 2016)"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp151"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.21037\/jgo.2016.01.05"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.12139"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.4103\/0975-1483.90245"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-012-9351-2"},{"key":"e_1_2_16_18_1","first-page":"3584","article-title":"Mechanisms of human tumor metastasis studied in patients with peritoneovenous shunts","volume":"44","author":"Tarin D","year":"1984","journal-title":"Cancer Res"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i41.6979"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2007.12.022"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.7-suppl_5-20"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157196"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/720858"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2006.02.029"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(89)90296-2"},{"key":"e_1_2_16_26_1","first-page":"2837","article-title":"Experimental and clinical evaluation of cisplatin\u2010containing microspheres as intraperitoneal chemotherapy for ovarian cancer","volume":"18","author":"Sugiyama T","year":"1998","journal-title":"Anticancer Res"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-003-0481-3"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2591"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2614"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2015.05.005"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2013.09.014"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1257"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00125"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja807416t"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3nr00114h"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.02.037"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(07)35015-5"},{"key":"e_1_2_16_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp200367s"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2015-0023"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.09.059"},{"key":"e_1_2_16_41_1","article-title":"Tunable resistive pulse sensing and nanoindentation of pH\u2010responsive expansile nanoparticles","author":"Weatherall E","year":"2016","journal-title":"Int J Nanotechnol"},{"key":"e_1_2_16_42_1","first-page":"2141","article-title":"Pharmacodynamics of immediate and delayed effects of paclitaxel: role of slow apoptosis and intracellular drug retention","volume":"58","author":"Au JL\u2010S","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_16_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm400434h"},{"key":"e_1_2_16_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.06.031"},{"key":"e_1_2_16_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2015.02.020"},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.6b06777"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2521"},{"key":"e_1_2_16_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-07-2117"},{"key":"e_1_2_16_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.82"},{"key":"e_1_2_16_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.140095"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.4776"},{"key":"e_1_2_16_52_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.3494"},{"key":"e_1_2_16_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2005.11.013"},{"key":"e_1_2_16_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.20013"},{"key":"e_1_2_16_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.21060"},{"key":"e_1_2_16_56_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-012-2696-5"},{"key":"e_1_2_16_57_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567201043480036"},{"key":"e_1_2_16_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3597"},{"key":"e_1_2_16_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3184"},{"key":"e_1_2_16_60_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.14951"},{"key":"e_1_2_16_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.11.038"},{"key":"e_1_2_16_62_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020128"},{"key":"e_1_2_16_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.11.038"},{"key":"e_1_2_16_64_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-210344"},{"key":"e_1_2_16_65_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1204"},{"key":"e_1_2_16_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18720"},{"key":"e_1_2_16_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat3049"},{"key":"e_1_2_16_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909565107"},{"key":"e_1_2_16_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610298104"},{"key":"e_1_2_16_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn404083m"},{"key":"e_1_2_16_71_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413027111"},{"key":"e_1_2_16_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/np030498t"},{"key":"e_1_2_16_73_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.323.7304.115\/a"},{"key":"e_1_2_16_74_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-10-0645"},{"key":"e_1_2_16_75_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1575"},{"key":"e_1_2_16_76_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402243"},{"key":"e_1_2_16_77_1","unstructured":"GrinstaffMW Soon\u2010ShiongP WongM SandfordPA SuslickKS DesaiNP.Composition useful for in vivo delivery of biologics and methods employing same. US5498421; 1996."},{"key":"e_1_2_16_78_1","unstructured":"GrinstaffMW Soon\u2010ShiongP WongM SandfordPA SuslickKS DesaiNP.Methods for the preparation of pharmaceutically active agents for in vivo delivery. US5665382; 1997."},{"key":"e_1_2_16_79_1","unstructured":"DesaiNP Soon\u2010ShiongP SandfordPA GrinstaffMW SuslickKS.Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor. US5439686; 1995."},{"key":"e_1_2_16_80_1","unstructured":"Soon\u2010ShiongP DesaiNP GrinstaffMW SandfordPA SuslickKS.Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor. US5439686; 1995."},{"key":"e_1_2_16_81_1","unstructured":"Protein\u2010bound paclitaxel. Wikimedia Foundation Inc. Available fromhttps:\/\/en.wikipedia.org\/wiki\/Protein\u2010bound_paclitaxel."},{"key":"e_1_2_16_82_1","unstructured":"FDA. FDA Approves New Drug for the Most Common Type of Lung Cancer Drug Shows Survival Benefit; 2004."}],"container-title":["WIREs Nanomedicine and Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fwnan.1451","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/wnan.1451","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/wnan.1451","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/wnan.1451","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/wnan.1451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T05:48:47Z","timestamp":1749966527000},"score":1,"resource":{"primary":{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/10.1002\/wnan.1451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,9]]},"references-count":81,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1002\/wnan.1451"],"URL":"https:\/\/doi.org\/10.1002\/wnan.1451","archive":["Portico"],"relation":{},"ISSN":["1939-5116","1939-0041"],"issn-type":[{"value":"1939-5116","type":"print"},{"value":"1939-0041","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,9]]},"article-number":"e1451"}}