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This study demonstrated the efficacy of low\u2010power ultrasound\u2010stimulated microbubble (USMB) therapy in enhancing drug delivery and improving the TNBC microenvironment, with a focus on its relationship with nitric oxide (NO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 4T1 murine TNBC model was established. Multi\u2010parametric imaging techniques, including contrast\u2010enhanced ultrasound (CEUS), ultra\u2010resolution microscopy imaging (URM), and photoacoustic imaging (PAI) were innovatively combined to assess tumor perfusion, oxygenation, and drug delivery following USMB treatment. Epirubicin penetration and targeted intratumoral distribution were quantitatively analyzed using high\u2010performance liquid chromatography (HPLC) and CD31 immunofluorescence under confocal microscopy. NO inhibition experiments were conducted to evaluate the involvement of the endothelial NO synthase (eNOS)\/NO pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Group USMB significantly increased tumor perfusion within 4\u2009hours post\u2010treatment (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001), reduced perfusion\u2010deficient regions, and raised oxygenation to 1.4\u2010fold of baseline. Doxorubicin (Dox) concentration was 3.15\u2010fold higher than the chemotherapy group, with wider distribution. Blocking eNOS\/NO signaling markedly attenuated the perfusion\u2010enhancing effects of USMB, implicating NO as a key mediator.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>USMB improves the TNBC microenvironment and enhances drug delivery by promoting perfusion and oxygenation, likely via NO signaling. These findings support USMB as a promising strategy for TNBC combination therapy and highlight NO as a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jum.70174","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T15:24:13Z","timestamp":1768663453000},"page":"1379-1396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low\u2010Power Ultrasound With Microbubbles Improve Oxygenation and Doxorubicin Uptake in Hypoxic Triple\u2010Negative Breast Cancer"],"prefix":"10.1002","volume":"45","author":[{"given":"Yaqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ultrasound The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research  Nanjing 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