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Mater."],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tumor acidosis is a consequence of altered metabolism that primarily takes place due to lactate secretion from anaerobic glycolysis. As a result, many regions within the tumors are chronically hypoxic and acidic. To measure the intratumor pH dynamically, we have fabricated a biocompatible pH nanoparticle sensor using surface-enhanced Raman spectroscopy (SERS-pNPS) and monitored continuous pH levels in three-dimensional multicellular spheroids. The 3D multicellular spheroids were cultured using a micro-well array chip made of polydimethylsiloxane (PDMS). The SERS-pNPS were synthesized by linking 4-Mercaptobenzoic acid (4-MBA) to silver nanoparticles (AgNPs) of size 50 nm. The calibration curve demonstrates a linear correlation between the ratio of Raman peak intensities (1378 cm\n                    <jats:sup>\u22121<\/jats:sup>\n                    \/1620 cm\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) with the pH level. The sensor exhibits a detection limit of pH 4.4 and demonstrates linearity within the physiological pH range (pH 4.4\u2013pH 8.23). The SERS-pNPS was applied for pH measurement in different 3D co-cultured spheroid models such as lung cancer (A549-NIH3T3), breast cancer (MCF-NIH3T3), colon cancer (HCT8-NIH3T3) and mono-cultured spheroids using fibroblast (NIH3T3) cells. The detailed analysis indicated that the 3D co-cultured cancerous tumor models have 16% more acidic microenvironment as compared to 3D mono-cultured spheroid model. Also, a presence of a decreasing pH gradient from peripheral to the core region is observed in both the cases indicating acidosis in the core region. The SERS-pNPS platform facilitates a non-invasive and dynamic pH tracking, and thus offers an improved insight into the acidic microenvironment in various tumor models.\n                  <\/jats:p>","DOI":"10.1088\/1748-605x\/adf47f","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T22:52:04Z","timestamp":1753483924000},"page":"055003","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["SERS based pH nanosensors for\n                    <i>in-vitro<\/i>\n                    pH measurement in multicellular 3D tumour spheroids"],"prefix":"10.1088","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4548-5566","authenticated-orcid":true,"given":"Koyel","family":"Dey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkanagouda S","family":"Goudar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9403-2155","authenticated-orcid":true,"given":"Tuhin Subhra","family":"Santra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7654-6905","authenticated-orcid":true,"given":"Fan-Gang","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"bmmadf47fbib1","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.canlet.2014.04.001","article-title":"The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism","volume":"356","author":"Lu","year":"2015","journal-title":"Cancer Lett."},{"key":"bmmadf47fbib2","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/nature19364","article-title":"Ionic immune suppression within the tumour microenvironment limits T cell effector function","volume":"537","author":"Eil","year":"2016","journal-title":"Nature"},{"key":"bmmadf47fbib3","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1007\/s00418-008-0530-8","article-title":"The tumor microenvironment and its contribution to tumor evolution toward metastasis","volume":"130","author":"Lorusso","year":"2008","journal-title":"Histochem. 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