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In the present study we evaluated the PDT efficacy of an NIR absorbing chlorophyll derivative \u2018Cycloimide Purpurin-18 (CIPp-18)\u2019 in Human Breast carcinoma (MCF-7) and cervical adenocarcinoma (Hela) cells under normoxic and hypoxic conditions.\u00a0PDT\u00a0with CIPp-18 (2.0\u00a0\u00b5M, 3\u00a0h) and NIR light (700\u2009\u00b1\u200925\u00a0nm, 0.36\u20131.4\u00a0J \/cm\n                    <jats:sup>2<\/jats:sup>\n                    )\u00a0induced potent phototoxicity in both the cell lines.\u00a0Under hypoxic conditions, PDT induced\u2009~\u200932% and 42% phototoxicity\u00a0at LD\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0and LD\n                    <jats:sub>70<\/jats:sub>\n                    \u00a0light dose, respectively, which corresponds to phototoxic\u00a0dose\u00a0under normoxia.\u00a0CIPp-18 in neat buffer (pH 7.4)\u00a0showed\u00a0generation of\u00a0singlet oxygen (\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) as well as superoxide (O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\n                      <jats:bold>\u00b7<\/jats:bold>\n                      \u2013\n                    <\/jats:sup>\n                    ) radicals.\u00a0Studies on\u00a0ROS generation in cells using fluorescence probes and the effect of mechanistic probes of\u00a0\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2\u00a0<\/jats:sub>\n                    (Sodium Azide, Histidine, D\n                    <jats:sub>2<\/jats:sub>\n                    O) and free radicals (DMSO, Mannitol, Cyanocobalamin, SOD-PEG) on phototoxicity show that\u00a0\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u00a0plays\u00a0major role in phototoxicity under normoxia.\u00a0Whereas, under hypoxic conditions, PDT\u00a0led to\u00a0no significant generation of ROS\u00a0and\u00a0phototoxicity\u00a0remained unaffected by\u00a0cyanocobalamin, a quencher of O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\n                      <jats:bold>\u00b7<\/jats:bold>\n                      \u2013\n                    <\/jats:sup>\n                    . Moreover, CIPp-18\u00a0showed localization in cell membrane and\u00a0PDT led to\u00a0more pronounced\u00a0loss of membrane\u00a0permeability\u00a0in cells\u00a0under hypoxia\u00a0than for\u00a0normoxia. These results\u00a0demonstrate\u00a0that CIPp-18 is\u00a0suitable for PDT of cancer cells under\u00a0hypoxia\u00a0and\u00a0also suggest that phototoxicity under hypoxia\u00a0is mediated via\u00a0ROS-independent contact-dependent mechanism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s43630-024-00680-w","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T03:11:14Z","timestamp":1737169874000},"page":"149-164","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unravelling the modes of phototoxicity of NIR absorbing chlorophyll derivative in cancer cells under normoxic and hypoxic conditions"],"prefix":"10.1007","volume":"24","author":[{"given":"Sucharita","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7664-4492","authenticated-orcid":false,"given":"Alok","family":"Dube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shovan Kumar","family":"Majumder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,18]]},"reference":[{"key":"680_CR1","doi-asserted-by":"publisher","unstructured":"Agostinis, P., Berg, K., Cengel, K. 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