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While hyperthermia has long been exploited in medicine, how localized temperature gradients influence cellular fate remains poorly understood. Here, a dual\u2010function nanodiamond platform is introduced that integrates optically detected magnetic resonance (ODMR) thermometry with croconium\u2010dye\u2010based photothermal heating to precisely modulate temperature within endo\u2010lysosomal compartments of macrophages. Controlled intracellular hyperthermia triggers oxidative stress, transcriptional reprogramming, and polarization toward a pro\u2010inflammatory phenotype, as confirmed by immunofluorescence, flow cytometry, and transcriptomics. These findings reveal intracellular thermal gradients as active regulators of immune signaling and gene expression. By establishing a direct subcellular thermal trigger for immune activation, independent of the canonical heat\u2010shock pathway. This work introduces a quantum\u2010enabled strategy for probing and programming cellular thermodynamics at the nanoscale.<\/jats:p>","DOI":"10.1002\/adma.202517076","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T06:12:46Z","timestamp":1765174366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Single\u2010Cell Hyperthermia: Diamond Quantum Thermometry Reveals Thermal Control of Macrophage Polarization"],"prefix":"10.1002","volume":"38","author":[{"given":"Kaiqi","family":"Wu","sequence":"first","affiliation":[{"name":"Max Planck Institute for Polymer Research  Ackermannweg 10 55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Lu","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  Ackermannweg 10 55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ren","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  Ackermannweg 10 55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyadharshini","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Institute for Quantum Optics Ulm University  Albert\u2010Einstein\u2010Allee 11 89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazem","family":"Ebadi Jalal","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Medical Center of the Johannes Gutenberg University Mainz  Langenbeckstra\u00dfe 1 55131 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Klug","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Medical Center of the Johannes Gutenberg University Mainz  Langenbeckstra\u00dfe 1 55131 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Medical Center of the Johannes Gutenberg University Mainz  Langenbeckstra\u00dfe 1 55131 Mainz Germany"},{"name":"Research Center for Immunotherapy (FZI) University Medical Center Mainz  55131 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toszka","family":"Bohn","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Medical Center of the Johannes Gutenberg University Mainz  Langenbeckstra\u00dfe 1 55131 Mainz Germany"},{"name":"Research Center for Immunotherapy (FZI) University Medical Center Mainz  55131 Mainz Germany"},{"name":"German Cancer Consortium (DKTK)  69120 Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Bopp","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Medical Center of the Johannes Gutenberg University Mainz  Langenbeckstra\u00dfe 1 55131 Mainz Germany"},{"name":"Research Center for Immunotherapy (FZI) University Medical Center Mainz  55131 Mainz Germany"},{"name":"German Cancer Consortium (DKTK)  69120 Heidelberg Germany"},{"name":"University Cancer Center (UCT) Mainz University Medical Center Mainz  55131 Mainz Germany"},{"name":"Institute for Quantitative and Computational Biosciences (IQCB)  55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedor","family":"Jelezko","sequence":"additional","affiliation":[{"name":"Institute for Quantum Optics Ulm University  Albert\u2010Einstein\u2010Allee 11 89081 Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingke","family":"Wu","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  Ackermannweg 10 55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-7205","authenticated-orcid":false,"given":"Tanja","family":"Weil","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  Ackermannweg 10 55128 Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-005-0689-y"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/02656736.2012.677933"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003992"},{"key":"e_1_2_9_4_1","volume":"147","author":"Lee Y.","year":"2025","journal-title":"J. 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