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Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors, which restricts targeted therapies and contributes to poor survival. Conventional chemotherapeutics such as doxorubicin and cisplatin show limited efficacy, significant toxicity, and resistance, underscoring the need for alternative strategies.\n                      <jats:italic>Nerium oleander<\/jats:italic>\n                      , a traditional medicinal plant, has demonstrated anticancer activity through leaf extracts; however, the role of exosome-like nanoparticles derived from its flowers (NELNs) remains unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The therapeutic efficacy of NELNs was evaluated in the MDA-MB-231 TNBC cell line using\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in silico<\/jats:italic>\n                      approaches. Cytotoxicity was assessed by the MTT assay, while AO\/EtBr and DCFDA staining examined apoptosis and ROS generation through fluorescence microscopy. Flow cytometry was employed for apoptosis confirmation and cell cycle analysis. Network pharmacology integrating target prediction, PPI network construction, and functional enrichment analysis was performed, followed by molecular docking of NELN-encapsulated metabolites against predicted targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NELNs induced significant cytotoxicity, promoted apoptosis, and increased intracellular ROS levels in MDA-MB-231 cells. Flow cytometry confirmed apoptotic induction and revealed alterations in cell cycle progression. Pathway enrichment analysis of previously identified NELN-associated metabolites computationally highlighted arachidonic acid and linoleic acid metabolism, with cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP3A4) emerging as putative targets. Molecular docking predicted favorable binding interactions of NELN metabolites to these targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides preliminary evidence that flower-derived NELNs exerted antiproliferative and pro-apoptotic activity against MDA-MB-231 cells under the tested experimental conditions. Furthermore, network pharmacology analyses generated putative mechanistic insights into pathways relevant to TNBC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1863223","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:25:47Z","timestamp":1783657547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic assessment of Nerium oleander-derived exosome-like nanoparticles against triple-negative breast cancer: a preliminary in vitro and network pharmacology approach"],"prefix":"10.3389","volume":"16","author":[{"given":"Sreyoshi","family":"Routh","sequence":"first","affiliation":[{"name":"School of Bio Sciences and Technology, Vellore Institute of Technology","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomsy","family":"Joseph","sequence":"additional","affiliation":[{"name":"School of Bio Sciences and Technology, Vellore Institute of Technology","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arya","family":"Sreekumar","sequence":"additional","affiliation":[{"name":"School of Bio Sciences and Technology, Vellore Institute of Technology","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatraman","family":"Manickam","sequence":"additional","affiliation":[{"name":"School of Bio Sciences and Technology, Vellore Institute of Technology","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2024.103835","article-title":"Current and future burden of breast cancer in Asia: A GLOBOCAN data analysis for 2022 and 2050.","volume":"79","author":"Fu","year":"2025","journal-title":"The Breast."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174287","article-title":"Breast cancer-epidemiology, risk factors, classification, prognostic markers, and current treatment strategies-an updated review","volume":"13","author":"\u0141ukasiewicz","year":"2021","journal-title":"Cancers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-014-4279-0","article-title":"The 2014 Society of Surgical Oncology Susan G. 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