{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:04:30Z","timestamp":1789621470635,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15CA268200"],"award-info":[{"award-number":["R15CA268200"]}],"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"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>5\u2010Aminolevulinic acid (ALA) is administered as a prodrug for tumor fluorescence detection and photodynamic therapy (PDT) after being converted endogenously to the active drug protoporphyrin IX (PpIX). As a substrate of the ABCG2 transporter, PpIX is subject to outward transport in cells with ABCG2 expression, resulting in reduced PpIX fluorescence and PDT effect. Due to the lack of approved ABCG2 inhibitors, lapatinib (Lap), a kinase inhibitor approved for cancer treatment, has been repurposed as an ABCG2 inhibitor for the enhancement of ALA. To provide evidence that Lap enhances ALA by inhibiting ABCG2, we knocked down ABCG2 in four tumor cell lines and evaluated the effects of Lap on enhancing ALA\u2010PpIX fluorescence and PDT in the wild\u2010type and ABCG2\u2010knockdown cell lines. ABCG2 knockdown enhanced ALA\u2010PpIX fluorescence and PDT response, underscoring the importance of ABCG2 in regulating intracellular PpIX accumulation. However, compared with the corresponding wild\u2010type cell lines, Lap induced less enhancement of PpIX fluorescence and PDT in ABCG2\u2010knockdown cell lines, particularly at high concentrations and in cell lines with low ABCG2 activities. By downregulating ABCG2 in tumor cells, we showed that Lap\u2010induced ALA enhancement was reduced, demonstrating that Lap enhances ALA by blocking ABCG2\u2010mediated PpIX efflux.<\/jats:p>","DOI":"10.1111\/php.70157","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:41:47Z","timestamp":1789620107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of\n                    <scp>ABCG2<\/scp>\n                    knockdown on therapeutic enhancement of 5\u2010aminolevulinic acid with lapatinib"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3386-4835","authenticated-orcid":false,"given":"Jordyn","family":"Wescoat","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy Saint Joseph's University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5966-321X","authenticated-orcid":false,"given":"Corinna","family":"Cabral","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy Saint Joseph's University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7736-4158","authenticated-orcid":false,"given":"Bin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy Saint Joseph's University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/bioengineering10040496","article-title":"5\u2010Aminolevulinic acid as a theranostic agent for tumor fluorescence imaging and photodynamic therapy","volume":"10","author":"Howley R","year":"2023","journal-title":"Bioengineering (Basel)"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.canlet.2020.06.008","article-title":"Clinical uses of 5\u2010aminolaevulinic acid in photodynamic treatment and photodetection of cancer: a review","volume":"490","author":"Casas A","year":"2020","journal-title":"Cancer Lett"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","DOI":"10.1117\/1.JBO.30.S3.S34112","article-title":"Emerging uses of 5\u2010aminolevulinic\u2010acid\u2010induced protoporphyrin IX in medicine: a review of multifaceted, ubiquitous, molecular diagnostic, therapeutic, and theranostic opportunities","volume":"30","author":"Pogue BW","year":"2025","journal-title":"J Biomed Opt"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1182\/blood-2004-04-1566","article-title":"Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX levels","volume":"105","author":"Zhou S","year":"2005","journal-title":"Blood"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2023.115851","article-title":"Targeting ABCG2 transporter to enhance 5\u2010aminolevulinic acid for tumor visualization and photodynamic therapy","volume":"217","author":"Chandratre S","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4161\/cbt.4.2.1440","article-title":"ABCG2\u2010mediated transport of photosensitizers: potential impact on photodynamic therapy","volume":"4","author":"Robey RW","year":"2005","journal-title":"Cancer Biol Ther"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0050082","article-title":"Mitochondrial localization of ABC transporter ABCG2 and its function in 5\u2010aminolevulinic acid\u2010mediated protoporphyrin IX accumulation","volume":"7","author":"Kobuchi H","year":"2012","journal-title":"PLoS One"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","DOI":"10.1038\/srep13298","article-title":"ABCG2 transporter inhibitor restores the sensitivity of triple negative breast cancer cells to aminolevulinic acid\u2010mediated photodynamic therapy","volume":"5","author":"Palasuberniam P","year":"2015","journal-title":"Sci Rep"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41568-018-0005-8","article-title":"Revisiting the role of ABC transporters in multidrug\u2010resistant cancer","volume":"18","author":"Robey RW","year":"2018","journal-title":"Nat Rev Cancer"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2023.101011","article-title":"Perspectives on drug repurposing to overcome cancer multidrug resistance mediated by ABCB1 and ABCG2","volume":"71","author":"Wu CP","year":"2023","journal-title":"Drug Resist Updat"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jphotobiol.2020.112017","article-title":"Evaluation of aminolevulinic acid\u2010mediated protoporphyrin IX fluorescence and enhancement by ABCG2 inhibitors in renal cell carcinoma cells","volume":"211","author":"Howley R","year":"2020","journal-title":"J Photochem Photobiol B"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2022.115031","article-title":"Inhibition of ABCG2 transporter by lapatinib enhances 5\u2010aminolevulinic acid\u2010mediated protoporphyrin IX fluorescence and photodynamic therapy response in human glioma cell lines","volume":"200","author":"Mansi M","year":"2022","journal-title":"Biochem Pharmacol"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/php.13936","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","volume":"100","author":"Howley R","year":"2024","journal-title":"Photochem Photobiol"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1111\/php.13982","article-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","volume":"100","author":"Kumbham S","year":"2024","journal-title":"Photochem Photobiol"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1158\/0008-5472.CAN-03-3298","article-title":"Pheophorbide a is a specific probe for ABCG2 function and inhibition","volume":"64","author":"Robey RW","year":"2004","journal-title":"Cancer Res"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1124\/jpet.115.225482","article-title":"The inhibitor Ko143 is not specific for ABCG2","volume":"354","author":"Weidner 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