{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T16:41:16Z","timestamp":1787935276721,"version":"build-2784847793"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21834002"],"award-info":[{"award-number":["21834002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The high rates of metastasis and recurrence in triple-negative breast cancer (TNBC) underscore the limitations of current therapies. Solamargin (SM), a bioactive glycoside, possesses potential antitumor activity, but its efficacy is limited by low potency and off-target effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We engineered Au@PEG-SM, a nanoconjugate designed for targeted delivery. Beyond traditional direct killing, we employed vascular endothelial cell models, STING-specific inhibitors (H-151), and cytokine neutralization assays to rigorously validate the molecular mechanism. Systemic immune profiling, including the analysis of lymph node dendritic cells, and bilateral tumor models were used to assess antitumor efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Au@PEG-SM synergizes with photothermal therapy (PTT) to achieve a potent 1 plus 1 greater than 2 therapeutic effect. Mechanistically, low-dose SM sensitizes the cGAS-STING pathway in vascular endothelial cells; upon synergistic activation by PTT-released DNA, this triggers a massive secretion of IFN-\u03b2 and TNF-\u03b1, leading to indirect tumor cell apoptosis. This process, combined with robust immunogenic cell death (ICD) and promoted dendritic cell maturation in lymph nodes, triggers a systemic antitumor response. Comprehensive immune profiling revealed that this combination therapy significantly increases the infiltration of NK cells and CD8\u2009+\u2009T cells while markedly reducing immunosuppressive MDSCs and regulatory T cells (Tregs) in both primary and distant tumors. When combined with anti-PD-L1 blockade, the therapy eradicated primary tumors and established durable immune memory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study establishes Au@PEG-SM as a powerful platform that achieves systemic immune activation via a sensitized STING-secretome-DC cascade. By providing rigorously validated mechanistic insights and a holistic immune landscape, our work offers a promising multimodal paradigm for overcoming TNBC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12282-026-01849-0","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T13:17:19Z","timestamp":1775049439000},"page":"705-721","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Solamargin-functionalized gold nanoparticles codelivering photothermal-immunotherapy for triple-negative breast cancer"],"prefix":"10.1007","volume":"33","author":[{"given":"Zhengwei","family":"Gui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7956-2257","authenticated-orcid":false,"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"issue":"1","key":"1849_CR1","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12\u201349.","journal-title":"CA Cancer J Clin"},{"issue":"8","key":"1849_CR2","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41568-020-0266-x","volume":"20","author":"KL Britt","year":"2020","unstructured":"Britt KL, Cuzick J, Phillips KA. Key steps for effective breast cancer prevention. Nat Rev Cancer. 2020;20(8):417\u201336.","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"1849_CR3","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s43556-022-00071-6","volume":"3","author":"R Yang","year":"2022","unstructured":"Yang R, Li Y, Wang H, Qin T, Yin X, Ma X. Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy. Mol Biomed. 2022;3(1):8.","journal-title":"Mol Biomed"},{"key":"1849_CR4","doi-asserted-by":"crossref","unstructured":"Vagia E, Mahalingam D, Cristofanilli M. The Landscape of Targeted Therapies in TNBC. Cancers (Basel) 2020;12(4).","DOI":"10.3390\/cancers12040916"},{"issue":"4","key":"1849_CR5","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1002\/mc.23389","volume":"61","author":"Q Tang","year":"2022","unstructured":"Tang Q, Li X, Chen Y, et al. Solamargine inhibits the growth of hepatocellular carcinoma and enhances the anticancer effect of sorafenib by regulating HOTTIP-TUG1\/miR-4726-5p\/MUC1 pathway. Mol Carcinog. 2022;61(4):417\u201332.","journal-title":"Mol Carcinog"},{"issue":"6","key":"1849_CR6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/carcin\/bgad028","volume":"44","author":"Q Tang","year":"2023","unstructured":"Tang Q, Zhou Q, Li J, et al. Solamargine enhanced gefitinib antitumor effect via regulating MALAT1\/miR-141-3p\/Sp1\/IGFBP1 signaling pathway in non-small cell lung cancer. Carcinogenesis. 2023;44(6):497\u2013510.","journal-title":"Carcinogenesis"},{"issue":"6","key":"1849_CR7","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1517\/14740338.2012.726610","volume":"11","author":"W Lv","year":"2012","unstructured":"Lv W, Piao JH, Jiang JG. Typical toxic components in traditional Chinese medicine. Expert Opin Drug Saf. 2012;11(6):985\u20131002.","journal-title":"Expert Opin Drug Saf"},{"issue":"8","key":"1849_CR8","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1142\/S0192415X1550086X","volume":"43","author":"LH Zha","year":"2015","unstructured":"Zha LH, He LS, Lian FM, et al. Clinical Strategy for Optimal Traditional Chinese Medicine (TCM) Herbal Dose Selection in Disease Therapeutics: Expert Consensus on Classic TCM Herbal Formula Dose Conversion. Am J Chin Med. 2015;43(8):1515\u201324.","journal-title":"Am J Chin Med"},{"key":"1849_CR9","doi-asserted-by":"publisher","first-page":"112668","DOI":"10.1016\/j.jep.2020.112668","volume":"253","author":"M Yang","year":"2020","unstructured":"Yang M, Wang L, Zhang T, et al. Different proteomic profiles of cinnabar upon therapeutic and toxic exposure reveal distinctive biological manifestations. J Ethnopharmacol. 2020;253:112668.","journal-title":"J Ethnopharmacol"},{"issue":"4","key":"1849_CR10","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1039\/D4TB02091J","volume":"13","author":"Y Zhou","year":"2025","unstructured":"Zhou Y, Wang L, Sun L, Tan R, Wang Z, Pei R. Progress in Chinese medicine monomers and their nanoformulations on myocardial ischemia\/reperfusion injury. J Mater Chem B. 2025;13(4):1159\u201379.","journal-title":"J Mater Chem B"},{"key":"1849_CR11","doi-asserted-by":"publisher","first-page":"e19332","DOI":"10.7717\/peerj.19332","volume":"13","author":"B Song","year":"2025","unstructured":"Song B, Shuang L, Zhang S, et al. Research progress of nano drug delivery systems in the anti-tumor treatment of traditional Chinese medicine monomers. PeerJ. 2025;13:e19332.","journal-title":"PeerJ"},{"issue":"5","key":"1849_CR12","doi-asserted-by":"publisher","first-page":"101131","DOI":"10.1016\/j.jpha.2024.101131","volume":"15","author":"C Pang","year":"2025","unstructured":"Pang C, Zhang J, Gu Y, Zhang Q, Zhao Y. The biological roles of exosome-encapsulated traditional Chinese medicine monomers in neuronal disorders. J Pharm Anal. 2025;15(5):101131.","journal-title":"J Pharm Anal"},{"issue":"1","key":"1849_CR13","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13045-022-01248-w","volume":"15","author":"S Yin","year":"2022","unstructured":"Yin S, Jin W, Qiu Y, Fu L, Wang T, Yu H. Solamargine induces hepatocellular carcinoma cell apoptosis and autophagy via inhibiting LIF\/miR-192-5p\/CYR61\/Akt signaling pathways and eliciting immunostimulatory tumor microenvironment. J Hematol Oncol. 2022;15(1):32.","journal-title":"J Hematol Oncol"},{"key":"1849_CR14","doi-asserted-by":"publisher","first-page":"216507","DOI":"10.1016\/j.canlet.2023.216507","volume":"582","author":"G Chen","year":"2024","unstructured":"Chen G, Zheng D, Zhou Y, Du S, Zeng Z. Olaparib enhances radiation-induced systemic anti-tumor effects via activating STING-chemokine signaling in hepatocellular carcinoma. Cancer Lett. 2024;582:216507.","journal-title":"Cancer Lett"},{"issue":"10","key":"1849_CR15","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.neo.2019.08.003","volume":"21","author":"J Riegler","year":"2019","unstructured":"Riegler J, Gill H, Ogasawara A, et al. VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models. Neoplasia. 2019;21(10):1036\u201350.","journal-title":"Neoplasia"},{"issue":"1","key":"1849_CR16","doi-asserted-by":"publisher","first-page":"2472308","DOI":"10.1080\/19336918.2025.2472308","volume":"19","author":"LE Chriqui","year":"2025","unstructured":"Chriqui LE, Cavin S, Perentes JY. Dual implication of endothelial adhesion molecules in tumor progression and cancer immunity. Cell Adh Migr. 2025;19(1):2472308.","journal-title":"Cell Adh Migr"},{"issue":"20","key":"1849_CR17","doi-asserted-by":"publisher","first-page":"5520","DOI":"10.1158\/1078-0432.CCR-11-2904","volume":"18","author":"Q Chen","year":"2012","unstructured":"Chen Q, Massague J. Molecular pathways: VCAM-1 as a potential therapeutic target in metastasis. Clin Cancer Res. 2012;18(20):5520\u20135.","journal-title":"Clin Cancer Res"},{"issue":"5","key":"1849_CR18","first-page":"2363","volume":"12","author":"Z Xue","year":"2022","unstructured":"Xue Z, Zheng S, Linghu D, et al. PD-L1 deficiency sensitizes tumor cells to DNA-PK inhibition and enhances cGAS-STING activation. Am J Cancer Res. 2022;12(5):2363\u201375.","journal-title":"Am J Cancer Res"},{"issue":"5","key":"1849_CR19","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.ijrobp.2021.12.162","volume":"112","author":"SS Du","year":"2022","unstructured":"Du SS, Chen GW, Yang P, et al. Radiation Therapy Promotes Hepatocellular Carcinoma Immune Cloaking via PD-L1 Upregulation Induced by cGAS-STING Activation. Int J Radiat Oncol Biol Phys. 2022;112(5):1243\u201355.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"12","key":"1849_CR20","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1158\/2326-6066.CIR-23-0902","volume":"12","author":"BG Kim","year":"2024","unstructured":"Kim BG, Kim BR, Kim DY, et al. Cannabidiol Enhances Atezolizumab Efficacy by Upregulating PD-L1 Expression via the cGAS-STING Pathway in Triple-Negative Breast Cancer Cells. Cancer Immunol Res. 2024;12(12):1796\u2013807.","journal-title":"Cancer Immunol Res"},{"key":"1849_CR21","doi-asserted-by":"crossref","unstructured":"Lee J. Current Treatment Landscape for Early Triple-Negative Breast Cancer (TNBC). J Clin Med 2023;12(4).","DOI":"10.3390\/jcm12041524"},{"issue":"6","key":"1849_CR22","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/j.cell.2018.08.027","volume":"174","author":"SF Bakhoum","year":"2018","unstructured":"Bakhoum SF, Cantley LC. The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment. Cell. 2018;174(6):1347\u201360.","journal-title":"Cell"},{"issue":"6","key":"1849_CR23","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1158\/2159-8290.CD-18-1218","volume":"9","author":"C Pantelidou","year":"2019","unstructured":"Pantelidou C, Sonzogni O, De Oliveria Taveira M, et al. PARP Inhibitor Efficacy Depends on CD8(+) T-cell Recruitment via Intratumoral STING Pathway Activation in BRCA-Deficient Models of Triple-Negative Breast Cancer. Cancer Discov. 2019;9(6):722\u201337.","journal-title":"Cancer Discov"},{"key":"1849_CR24","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.actbio.2023.02.011","volume":"160","author":"X Feng","year":"2023","unstructured":"Feng X, Lin T, Chen D, et al. Mitochondria-associated ER stress evokes immunogenic cell death through the ROS-PERK-eIF2alpha pathway under PTT\/CDT combined therapy. Acta Biomater. 2023;160:211\u201324.","journal-title":"Acta Biomater"},{"key":"1849_CR25","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.jcis.2024.02.100","volume":"663","author":"H Lin","year":"2024","unstructured":"Lin H, Jiang C, Wang B, et al. Glutathione degradable manganese-doped polydopamine nanoparticles for photothermal therapy and cGAS-STING activated immunotherapy of lung tumor. J Colloid Interface Sci. 2024;663:167\u201376.","journal-title":"J Colloid Interface Sci"}],"container-title":["Breast Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12282-026-01849-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12282-026-01849-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12282-026-01849-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:20:22Z","timestamp":1781644822000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12282-026-01849-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["1849"],"URL":"https:\/\/doi.org\/10.1007\/s12282-026-01849-0","relation":{},"ISSN":["1340-6868","1880-4233"],"issn-type":[{"value":"1340-6868","type":"print"},{"value":"1880-4233","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"assertion":[{"value":"18 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All animal experiments were conducted in accordance with protocols approved by the Animal Care and Use Committee of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology (Approval document: TJH-243688). All necessary ethical regulations were strictly adhered to during the experiments.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}