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Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of melanin contribution to melanoma resistance to PDT was investigated in a set of melanoma cell lines that markedly differ in the levels of pigmentation;3 new bacteriochlorins successfully overcame the resistance. Cell killing studies determined that bacteriochlorins are superior at (LD\n                    <jats:sub>50<\/jats:sub>\n                    \u22480.1 \u00b5M) when compared with controls such as the FDA\u2010approved Photofrin (LD\n                    <jats:sub>50<\/jats:sub>\n                    \u224810 \u00b5M) and clinically tested LuTex (LD\n                    <jats:sub>50<\/jats:sub>\n                    \u2248=1 \u00b5M). The melanin content affects PDT effectiveness, but the degree of reduction is significantly lower for bacteriochlorins than for Photofrin. Microscopy reveals that the least effective bacteriochlorin localizes predominantly in lysosomes, while the most effective one preferentially accumulates in mitochondria. Interestingly all bacteriochlorins accumulate in melanosomes, and subsequent illumination leads to melanosomal damage shown by electron microscopy. Fluorescent probes show that the most effective bacteriochlorin produces significantly higher levels of hydroxyl radicals, and this is consistent with the redox properties suggested by molecular\u2010orbital calculations. The best\n                    <jats:italic>in vitro<\/jats:italic>\n                    performing bacteriochlorin was tested\n                    <jats:italic>in vivo<\/jats:italic>\n                    in a mouse melanoma model using spectrally resolved fluorescence imaging and provided significant survival advantage with 20% of cures (\n                    <jats:italic>P&lt;<\/jats:italic>\n                    0.01).\u2014Mroz, P., Huang, Y.\u2010Y., Szokalska, A., Zhiyentayev, T., Janjua, S., Nifli, A.\u2010P., Sherwood, M. E., Ruzi\u00e9, C., Borbas, K. E., Fan, D., Krayer, M., Balasubramanian, T., Yang, E., Kee, H. L., Kirmaier, C., Diers, J. R., Bocian, D. F., Holten, D., Lindsey, J. S., Hamblin, M. R. Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 24, 3160\u20133170 (2010).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.09-152587","type":"journal-article","created":{"date-parts":[[2010,4,12]],"date-time":"2010-04-12T22:28:20Z","timestamp":1271111300000},"page":"3160-3170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy"],"prefix":"10.1096","volume":"24","author":[{"given":"Pawel","family":"Mroz","sequence":"first","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Dermatology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Dermatology Harvard Medical School  Boston Massachusetts USA"},{"name":"Aesthetic and Plastic Center Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Szokalska","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Immunology Center of Biostructure Medical University of Warsaw  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timur","family":"Zhiyentayev","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Chemistry Department Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Janjua","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Aga Khan Medical College  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artemissia\u2010Phoebe","family":"Nifli","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Department of Dermatology Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Sherwood","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Ruzi\u00e9","sequence":"additional","affiliation":[{"name":"Department of Chemistry North Carolina State University  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Eszter","family":"Borbas","sequence":"additional","affiliation":[{"name":"Department of Chemistry North Carolina State University  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhong","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Chemistry North Carolina State University  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Krayer","sequence":"additional","affiliation":[{"name":"Department of Chemistry North Carolina State University  Raleigh North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiagarajan","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"NIRvana Pharmaceuticals, Inc.  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