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Symptoms of photosensitivity manifest as erythema and edema on skin exposed to sunlight or bright artificial lighting. Recent efforts using nanocarriers to increase photosensitizer accumulation in tumors have also been shown to reduce skin photosensitivity. We previously developed phototheranostic PORPHYSOME (PS) nanoparticles self\u2010assembled from porphyrin\u2013lipid conjugates and capable of potent anti\u2010tumor PDT. Here, we demonstrate in a nonpigmented rat skin model that PS exhibit less severe and shorter\u2010lasting skin photosensitivity compared with an equivalent drug dose of porfimer sodium (PHO), the canonical first\u2010generation PDT drug. At 2, 4, 8, and 12\u2009days post intravenous injection, depilated skin was exposed to escalating doses of simulated solar light. Light exposure 4\u2009days post\u2010injection showed markedly reduced symptoms of skin photosensitivity with PS than PHO. By Day 8, the minimal dose of light eliciting any kind of skin reaction was significantly higher with PS than PHO, and by Day 12, there was no detectable skin response with PS. These differences were attributed to altered intradermal distribution and faster clearance of PS vs. PHO in rat skin.<\/jats:p>","DOI":"10.1111\/php.14088","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T07:40:04Z","timestamp":1744011604000},"page":"1541-1558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cutaneous photosensitivity of phototheranostic porphyrin\u2013lipid nanoparticles"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3488-023X","authenticated-orcid":false,"given":"Michael S.","family":"Valic","sequence":"first","affiliation":[{"name":"Princess Margaret Cancer Centre University Health Network  Toronto Ontario Canada"},{"name":"Institute of Biomedical Engineering University of Toronto  Toronto Ontario 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