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Its effectiveness is governed by the oxygen content, which is scarce in the hypoxic tumor microenvironment. We report herein two zinc(II) phthalocyanines substituted with two or four nitric oxide (NO)\u2010releasing moieties, namely\n                    <jats:bold>ZnPc\u20102NO<\/jats:bold>\n                    and\n                    <jats:bold>ZnPc\u20104NO<\/jats:bold>\n                    , which can suppress the mitochondrial respiration, thereby sparing more intracellular oxygen for PDT. Using HT29 human colorectal adenocarcinoma cells and A549 human lung carcinoma cells, we have demonstrated that both conjugates release NO upon interaction with the intracellular glutathione, which can reduce the cellular oxygen consumption rate and adenosine triphosphate generation and alter the mitochondrial membrane potential. They can also relieve the hypoxic status of cancer cells and decrease the expression of hypoxia\u2010inducible factor protein HIF\u20101\u03b1. Upon light irradiation, both conjugates can generate ROS and induce cytotoxicity even under a hypoxic condition, overcoming the oxygen\u2010dependent nature of PDT. Interestingly, the photodynamic action of\n                    <jats:bold>ZnPc\u20102NO<\/jats:bold>\n                    elicits the release of damage\u2010associated molecular patterns, inducing the maturation of dendritic cells and triggering an antitumor immune response. The immunogenic cell death caused by this oxygen\u2010economized PDT has been demonstrated through a series of in vitro and in vivo experiments.\n                  <\/jats:p>","DOI":"10.1002\/anie.202404561","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T05:03:56Z","timestamp":1718687036000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Inducing Immunogenic Cancer Cell Death through Oxygen\u2010Economized Photodynamic Therapy with Nitric Oxide\u2010Releasing Photosensitizers"],"prefix":"10.1002","volume":"63","author":[{"given":"Feijie","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Tung Biomedical Sciences Centre City University of Hong Kong Kowloon  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Tung Biomedical Sciences Centre City University of Hong Kong Kowloon  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Dotse","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Tung Biomedical Sciences Centre City University of Hong Kong Kowloon  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan T.","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Tung Biomedical Sciences Centre City University of Hong Kong Kowloon  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0315-8538","authenticated-orcid":false,"given":"Pui\u2010Chi","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Tung Biomedical Sciences Centre City University of Hong Kong Kowloon  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174447"},{"key":"e_1_2_7_2_1","unstructured":"\u00a0"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201805246"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25225317"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.06.019"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2022.138621"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00381"},{"key":"e_1_2_7_8_1","unstructured":"\u00a0"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.16183"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15020330"},{"key":"e_1_2_7_11_1","unstructured":"\u00a0"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2468"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3726"},{"key":"e_1_2_7_14_1","unstructured":"\u00a0"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201805138"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph12040163"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2021.213888"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41427-021-00303-1"},{"key":"e_1_2_7_19_1","unstructured":"\u00a0"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9785"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep23393"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b04371"},{"key":"e_1_2_7_23_1","unstructured":"\u00a0"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.7b02533"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b05559"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201706375"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b11114"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b01087"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202010005"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0BM00187B"},{"key":"e_1_2_7_31_2","first-page":"51","volume":"162","author":"He L.","year":"2023","journal-title":"Acta Biomater."},{"key":"e_1_2_7_32_1","unstructured":"\u00a0"},{"key":"e_1_2_7_33_2","first-page":"1784","volume":"13","author":"Yu W. 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