{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:31:45Z","timestamp":1789662705848,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201017\u20101\u20100226"],"award-info":[{"award-number":["W81XWH\u201017\u20101\u20100226"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA268390"],"award-info":[{"award-number":["R01CA268390"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Photochem &amp; Photobiology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Protoporphyrin IX (PpIX)\u2010based photodynamic therapy (PDT) has shown limited efficacy in nonmuscle\u2010invasive bladder cancer (NMIBC). To improve PDT efficacy, we developed singlet oxygen\u2010cleavable prodrugs. These prodrugs, when combined with PpIX\u2010PDT, induce cancer cell death through both PDT and drug release mechanisms. Inhibition of PpIX efflux was reported to be an effective strategy to improve PpIX\u2010PDT in certain cancer cells. Our main goal was to investigate whether adding an efflux inhibitor to the combination of PpIX and prodrugs can improve the PpIX levels in bladder cancer cells and the release of active drugs, thus improving the overall efficacy of the treatment. We treated bladder cancer cell lines with lapatinib and evaluated intracellular PpIX fluorescence, finding significantly increased accumulation. Combining lapatinib with prodrugs led to significantly reduced cell viability compared to prodrugs or PpIX\u2010PDT alone. The effect of lapatinib depended on the expression level of the efflux pump in bladder cancer cells. Interestingly, lapatinib increased paclitaxel (PTX) prodrug uptake by threefold compared to prodrug alone. Adding an efflux inhibitor (e.g., lapatinib) into bladder instillation solutions could be a straightforward and effective strategy for NMIBC treatment, particularly in tumors expressing efflux pumps, with the potential for clinical translation.<\/jats:p>","DOI":"10.1111\/php.13982","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T02:45:06Z","timestamp":1718246706000},"page":"1636-1646","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhancing PDT efficacy in NMIBC: Efflux inhibitor mediated improvement of PpIX levels and efficacy of the combination of PpIX\u2010PDT and SO\u2010cleavable prodrugs"],"prefix":"10.1111","volume":"100","author":[{"given":"Soniya","family":"Kumbham","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo, The\u00a0State University of New York  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazi Md Mahabubur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo, The\u00a0State University of New York  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Bosmajian","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo, The\u00a0State University of New York  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Bist","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo, The\u00a0State University of New York  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Roswell Park Comprehensive Cancer Center  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukyung","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo, The\u00a0State University of New York  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0835-464X","authenticated-orcid":false,"given":"Youngjae","family":"You","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo, The\u00a0State University of New York  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31012-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2017.02.75"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.09.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00060"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13020166"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.06.045"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.5301\/uro.5000197"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1071"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20114"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)00701-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.13726"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2021.691697"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.049"},{"key":"e_1_2_8_16_1","first-page":"505","article-title":"Basic principles, applications in oncology and improved selectivity of photodynamic therapy","volume":"23","author":"Vrouenraets MB","year":"2003","journal-title":"Anticancer Res"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1562\/2006-02-03-IR-794"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.13291"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2019.03.053"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.JBO.26.9.098002"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161025865"},{"key":"e_1_2_8_22_1","first-page":"1","article-title":"Effectiveness of lapatinib for enhancing 5\u2010aminolevulinic acid\u2010mediated protoporphyrin IX fluorescence and photodynamic therapy in human cancer cell lines with varied ABCG2 activities","author":"Howley R","year":"2024","journal-title":"Photochem Photobiol"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13298"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2020.112017"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.4.2.1440"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2013.07.003"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2020.111963"},{"key":"e_1_2_8_28_1","first-page":"417","article-title":"Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in\u00a0vitro and in mouse intestine by a novel analogue of fumitremorgin C","volume":"1","author":"Allen JD","year":"2002","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.225482"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-014-9668-6"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115031"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2012.06.003"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1599"},{"key":"e_1_2_8_34_1","first-page":"1","article-title":"Preclinical evaluation of singlet oxygen\u2010cleavable prodrugs in combination with protoporphyrin IX\u2010photodynamic therapy in an orthotopic rat model of non\u2010muscle\u2010invasive bladder cancer","author":"Rahman KMM","year":"2023","journal-title":"Photochem Photobiol"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0499"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-5394.1999.07205.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3592"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2009.27.15_suppl.e20656"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12913-021-06425-0"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2017.02.003"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00168"}],"container-title":["Photochemistry and Photobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/php.13982","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T06:38:01Z","timestamp":1731739081000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/php.13982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,12]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/php.13982"],"URL":"https:\/\/doi.org\/10.1111\/php.13982","archive":["Portico"],"relation":{},"ISSN":["0031-8655","1751-1097"],"issn-type":[{"value":"0031-8655","type":"print"},{"value":"1751-1097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,12]]},"assertion":[{"value":"2024-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}