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Despite encouraging clinical outcomes in glioblastoma and prostate cancer, the broader clinical translation of MFH across various tumor types remains limited by heterogeneous nanoparticle distribution, inconsistent tumor heating, and the frequent use of poorly predictive preclinical two-dimensional (2D) cultures. These conventional cultures fail to recapitulate the structural and stromal complexity of solid tumors and often overestimate therapeutic efficacy. In an attempt to recreate the cellular heterogeneity of clinical breast tumors to some extent, we developed a hetero-multicellular spheroid of breast cancer by co-culturing breast adenocarcinoma cells MCF-7, with non-cancerous murine fibroblasts McCoy. This approach generated heterospheroids that mimic certain key features of the breast tumor microenvironment, including heterogeneous cell population, fibroblast activation, collagen-rich extracellular matrix deposition, and the spatial arrangement of proliferative, quiescent, and necrotic cells. Following histologic validation, the hyperthermic potential of poly(acrylic acid)-coated Mn0.9Zn0.1Fe2O4 nanoparticle-based magnetic fluid on the heterospheroids was assessed under a 10 kA\/m magnetic field strength and 332 kHz frequency. A single-session MFH inhibited heterospheroid growth and induced apoptosis; however, it did not significantly ablate the spheroids. Subsequently, two MFH sessions led to the complete elimination of the spheroids, accompanied by pronounced apoptotic activity. These findings suggest that repeated MFH can overcome thermotolerance, thereby augmenting therapeutic potential against stromal-rich breast tumors.<\/jats:p>","DOI":"10.1021\/acsabm.6c00915","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:03:05Z","timestamp":1791817385000},"page":"10195-10208","source":"Crossref","is-referenced-by-count":0,"title":["Multiple-Session Magnetic Fluid Hyperthermia: Augmented MNPs Penetration Led to Complete Eradication of Hetero-Multicellular Breast Tumor Spheroids via Apoptosis"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9667-4563","authenticated-orcid":true,"given":"Tushar","family":"Patel","sequence":"first","affiliation":[{"name":"Charotar University of Science and Technology (CHARUSAT) , , CHARUSAT Campus, Changa , , ,","place":["Anand, Gujarat, India, 388 421"]},{"name":"Charotar University of Science and Technology (CHARUSAT) , , CHARUSAT Campus, Changa , , ,","place":["Anand, Gujarat, India, 388 421"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurang","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Gujarat University , , ,","place":["Ahmedabad, India, 380009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaid","family":"Johar","sequence":"additional","affiliation":[{"name":"Gujarat University , , ,","place":["Ahmedabad, India, 380009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1566-2846","authenticated-orcid":true,"given":"Kinnari H.","family":"Parekh","sequence":"additional","affiliation":[{"name":"Charotar University of Science and Technology (CHARUSAT) , , CHARUSAT Campus, Changa , , ,","place":["Anand, Gujarat, India, 388 421"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1415-3652","authenticated-orcid":true,"given":"Neeraj","family":"Jain","sequence":"additional","affiliation":[{"name":"Charotar University of Science and Technology (CHARUSAT) , , CHARUSAT Campus, Changa , , ,","place":["Anand, Gujarat, India, 388 421"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"issue":"3","key":"2026110201075803600_cit1","first-page":"1163","article-title":"Effect of pH on single or fractionated heat treatments at 42-45 degrees","volume":"43","author":"Gerweck","year":"1983","journal-title":"Cancer Res."},{"issue":"4","key":"2026110201075803600_cit2","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/s0167-8140(84)80077-8","article-title":"The relevance of tumour pH to the treatment of malignant disease","volume":"2","author":"Wike-Hooley","year":"1984","journal-title":"Radiother. 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