{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T20:24:53Z","timestamp":1770150293041,"version":"3.49.0"},"reference-count":50,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH403"],"award-info":[{"award-number":["ZR2021MH403"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Qingdao Municipal Demonstration Project for Science & Technology to Benefit the People","award":["25-1-5-smjk-13-nsh"],"award-info":[{"award-number":["25-1-5-smjk-13-nsh"]}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Biomater Res"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Triple-negative breast cancer (TNBC) remains therapeutically challenging owing to the paucity of broadly effective molecular targets. Piezoelectric nanomaterials that generate localized electric fields and reactive oxygen species under ultrasound (US) stimulation have emerged as a promising strategy for TNBC therapy. Here, we developed a US-activatable nanoplatform (HN-T\/BT@Lip) in which toyocamycin-loaded CaCO\n                    <jats:sub>3<\/jats:sub>\n                    \u2013carboxymethyl chitosan hybrid nanoparticles (HNs) and barium titanate (BaTiO\n                    <jats:sub>3<\/jats:sub>\n                    , BT) are co-encapsulated in folate-modified liposomes. US-activated HN-T\/BT@Lip suppressed tumor growth and induced ferroptosis. Integrated transcriptomic, metabolomic, and microbiota profiling further revealed that this treatment disrupts glutathione metabolism, enhances susceptibility to lipid peroxidation, and perturbs iron homeostasis. These effects were closely associated with shifts in microbial community composition and altered levels of microbiota-derived metabolites. In\u00a0vitro assays further demonstrated that the microbiota-associated metabolite trimethylamine\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -oxide synergistically amplified lipid peroxidation under HN-T\/BT@Lip + US treatment. Collectively, our findings demonstrate that US-activated HN-T\/BT@Lip elicits potent ferroptosis in TNBC while concomitantly reshaping the intratumoral microbiota\u2013metabolism landscape, and they highlight microbiota-derived metabolites such as trimethylamine\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    -oxide as potential modulators and biomarkers of nanotherapeutic ferroptosis.\n                  <\/jats:p>","DOI":"10.34133\/bmr.0317","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T22:43:01Z","timestamp":1767739381000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound-Activated Nanoplatform Counteracts Triple-Negative Breast Cancer via Remodeling Intratumoral Microbiota\u2013Metabolism and Inducing Ferroptosis"],"prefix":"10.34133","volume":"30","author":[{"given":"Shuao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxiu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danni","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao 266071, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningning","family":"He","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao 266071, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangyong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China."},{"name":"School of Basic Medicine, Qingdao Medical College, \rQingdao University, Qingdao 266071, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luxia","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7821-7755","authenticated-orcid":true,"given":"Cheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Abdominal Ultrasound, \rThe Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.34133\/bmr.0088"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.34133\/bmr.0258"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2023.5033"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.04.026"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S491816"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.37015\/AUDT.2024.240053"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-024-04740-0"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.102065"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202417564"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-025-02214-w"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123311"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c12668"},{"issue":"40","key":"e_1_3_4_14_2","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202401171","article-title":"Doping-engineered piezoelectric ultrathin nanosheets for synergistically piezo-chemocatalytic antitumor and antibacterial therapies against cutaneous melanoma","volume":"20","author":"Jing L","year":"2024","unstructured":"Jing L, Zhuang F, Feng W, Huang H, Chen Y, Huang B. Doping-engineered piezoelectric ultrathin nanosheets for synergistically piezo-chemocatalytic antitumor and antibacterial therapies against cutaneous melanoma. Small. 2024;20(40): Article e2401171.","journal-title":"Small"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104444"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322780"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.03.011"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc3421"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202206861"},{"key":"e_1_3_4_20_2","unstructured":"Zhang T Qiu Y Luo Q Cheng X Zhao L Yan X Peng B Jiang H Yang H. Concentration dependent effects of Ca2+ and Mg2+ on the phosphatidylethanolamine-phosphatidylglycerol bilayer. 2019;35(8):840\u2013849."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.36762"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S505526"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.34133\/research.0867"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/sia.2904"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/crat.202300022"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33711"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40824-023-00401-x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.113887"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12050804"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104533"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03297-w"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mattod.2025.09.019"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156195"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2012.02631.x"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/bab.2641"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.5c00637"},{"key":"e_1_3_4_37_2","first-page":"29","article-title":"Natural polyphenol-mediated inhibition of ferroptosis alleviates oxidative damage and inflammation in acute liver injury","author":"Su Y","year":"2025","unstructured":"Su Y, Zeng Y, Zhou M, Liao M, Qin P, Wu R, Han J, Liang X, Wang Z, Jiang J, et al. Natural polyphenol-mediated inhibition of ferroptosis alleviates oxidative damage and inflammation in acute liver injury. Biomater Res. 2025;29, Article 0167.","journal-title":"Biomater Res"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwaf002"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c00952"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c01968"},{"issue":"6","key":"e_1_3_4_41_2","first-page":"799","article-title":"Efficient synthesis strategy of folate-modified carboxymethyl chitosan\/CaCO3 hybrid nanospheres and their drug-carrying and sustained release properties, journal of biomaterials science","volume":"32","author":"Guo J","year":"2021","unstructured":"Guo J, Liu J, Qie H, Zhao F, Niu CH. Efficient synthesis strategy of folate-modified carboxymethyl chitosan\/CaCO3 hybrid nanospheres and their drug-carrying and sustained release properties, journal of biomaterials science. 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ACS Omega. 2024;9(11):12539\u201312552.","journal-title":"ACS Omega"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2023.106688"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.3390\/ma14164419"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S254745"}],"container-title":["Biomaterials Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/bmr.0317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T08:01:31Z","timestamp":1770105691000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.34133\/bmr.0317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":50,"alternative-id":["10.34133\/bmr.0317"],"URL":"https:\/\/doi.org\/10.34133\/bmr.0317","relation":{},"ISSN":["2055-7124"],"issn-type":[{"value":"2055-7124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"0317"}}