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Here, we investigate the biological application of core\u2013shell UCNPs functionalized with a photosensitizer for the intracellular generation of singlet oxygen (1O2). The nanoparticles exhibited reproducible morphology, phase purity, and strong upconversion emission intensity, enabling efficient activation under NIR excitation. Murine RAW 264.7 macrophages were employed as a model of innate immune cells to evaluate nanoparticle uptake, cytocompatibility, and light-triggered 1O2 production. Luminescence-based assays and microscopy analyses confirmed efficient cellular internalization and localized 1O2 generation upon low-energy NIR excitation, while cytotoxicity studies demonstrated low basal toxicity in the absence of irradiation. Upon photoactivation, a significant reduction in cell viability was observed, consistent with photodynamically induced oxidative stress. These results further demonstrate that UCNP-based nanoplatforms can function as effective intracellular generators of reactive oxygen species in phagocytic immune cells and highlight their potential for photodynamic therapy (PDT), redox modulation, and to study molecular interactions at the cell membrane level.<\/jats:p>","DOI":"10.1021\/acsomega.6c04049","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T20:02:23Z","timestamp":1788552143000},"page":"55412-55421","source":"Crossref","is-referenced-by-count":1,"title":["Intracellular Singlet\nOxygen Generation Mediated by\nUpconversion Nanoparticles in RAW 264.7 Macrophages"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6145-188X","authenticated-orcid":true,"given":"Amanda","family":"Annunciac\u0327a\u0303o Farhat","sequence":"first","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Paulo, Sa\u0303o Paulo, Brasil, BR-05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4140-5915","authenticated-orcid":true,"given":"Bernardina","family":"Amori\u0301n Uscata","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Paulo, Sa\u0303o Paulo, Brasil, BR- 05403-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2047-1136","authenticated-orcid":true,"given":"Magnus Ake","family":"Gidlund","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Paulo, Sa\u0303o Paulo, Brasil, BR-05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiro","family":"Goto","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Paulo, Sa\u0303o Paulo, Brasil, BR- 05403-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5438-1174","authenticated-orcid":true,"given":"Marisa Helena Gennari de","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Paulo, Sa\u0303o Paulo, Brasil, BR-05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-4441","authenticated-orcid":true,"given":"Hermi Felinto","family":"Brito","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Paulo, Sa\u0303o Paulo, Brasil, BR-05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-8350","authenticated-orcid":true,"given":"Paolo","family":"Di Mascio","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Paulo, Sa\u0303o Paulo, Brasil, BR-05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"issue":"12","key":"2026092210571039300_cit1","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1038\/nri1733","article-title":"Monocyte and Macrophage Heterogeneity","volume":"5","author":"Gordon","year":"2005","journal-title":"Nat. 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