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Here we engineer rsmiRFPnano, a compact cyanobacteriochrome-derived photoswitchable PAT probe. With a molecular weight below 19\u2009kDa, rsmiRFPnano efficiently incorporates biliverdin, exhibits high extinction coefficients in both photochromic states and demonstrates robust performance in live cells. We established rsmiRFPnano-based reporters for NF-\u03baB and AP-1 pathways, which display low basal activity and strong activation-dependent responses. These reporters effectively visualized acute inflammation using noninvasive PAT in vivo, further validated through cellular-level spatial omics mapping. We then created photoswitchable nanobody probes, rsNIR-Fbs, stabilized upon antigen binding and rapidly degraded otherwise, enabling selective photoacoustic immuno-imaging of intracellular antigens in vivo. Together, these results establish rsmiRFPnano as an ultracompact and versatile platform for molecular PAT.<\/jats:p>","DOI":"10.1038\/s41592-026-03255-y","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:38:10Z","timestamp":1791920290000},"page":"2274-2285","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Near-infrared photochromic miniprotein enables photoacoustic molecular imaging of acute inflammation and intracellular antigens"],"prefix":"10.1038","volume":"23","author":[{"given":"Olena S.","family":"Oliinyk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0123-0839","authenticated-orcid":false,"given":"Jinhuan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7160-5707","authenticated-orcid":false,"given":"Kateryna O.","family":"Tokarchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-5751","authenticated-orcid":false,"given":"Kyrylo Yu.","family":"Manoilov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie","family":"van de Klashorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9498-1182","authenticated-orcid":false,"given":"Matthew P.","family":"Eyring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-en","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-1062","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9103-6345","authenticated-orcid":false,"given":"Pengfei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-7673","authenticated-orcid":false,"given":"John W.","family":"Hickey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2381-706X","authenticated-orcid":false,"given":"Junjie","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2083-8121","authenticated-orcid":false,"given":"Vladislav V.","family":"Verkhusha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"3255_CR1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s44303-024-00048-w","volume":"2","author":"L Menozzi","year":"2024","unstructured":"Menozzi, L. & Yao, J. 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