{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:38:17Z","timestamp":1786541897347,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: This study engineered and evaluated a targeted, folate-functionalized chitosan nanoparticle (CS-FA NP) delivery system to enhance the therapeutic efficacy of standard quercetin and Coriandrum sativum seed extract against breast cancer. Methods: Phytochemical profiling confirmed a 14% crude yield for the methanolic extract, with gas chromatography\u2013mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) identifying quercetin as the principal bioactive agent. The synthesized CS-FA NPs exhibited a core size of 7\u201320 nm, an average hydrodynamic diameter of 150\u2013160 nm, a stable zeta potential of \u221255 mV, and high encapsulation efficiencies (87.2% for quercetin and 80.5% for coriander). Kinetic assessments confirmed a biphasic, diffusion-controlled release matching Higuchi matrix kinetics. Anticancer activity was evaluated in vitro using MTT cytotoxicity, Annexin V-FITC\/PI apoptosis analysis, RT-qPCR, and ex vivo rat aortic ring assays, followed by validation in a syngeneic 4T1 mammary tumor mouse model. Results: In vitro, folate-receptor-targeted quercetin nanoparticles (T4) demonstrated superior, selective cytotoxicity, particularly against triple-negative MDA-MB-231 cells, while sparing normal fibroblasts. Annexin V-FITC\/PI apoptosis profiling and ex vivo aortic ring assays revealed profound, cell-line-dependent programmed cell death and up to 90% inhibition of microvessel sprout outgrowth. Mechanistically, RT-qPCR verified that nano-formulations induced complete transcriptional silencing of NANOG, MMP-1, VEGFA, TSPAN8, TWIST, EMMPRIN, and CDK1, alongside marked upregulation of P27KIP1 and P21CIP1. In vivo, these nano-formulations successfully improved tumor-associated pathological features, reduced aggressive tumor spindle-cell proliferation, and suppressed elevated serum CA15-3 and arginase biomarkers. Conclusions: Folate-functionalized chitosan nano-formulations significantly enhanced the anticancer efficacy of quercetin and Coriandrum sativum seed extract through improved targeted delivery, potent antiproliferative, anti-angiogenic, and pro-apoptotic activities, together with favorable modulation of multiple molecular pathways associated with breast cancer progression. These findings support their potential as promising targeted nanotherapeutic strategies for breast cancer treatment.<\/jats:p>","DOI":"10.3390\/ph19081271","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:53:48Z","timestamp":1786539228000},"page":"1271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Folate-Chitosan Nanoformulations of Quercetin and Coriandrum sativum Reprogram Breast Cancer Hallmarks by Silencing Stemness, Cell Cycle, Angiogenic, and Metastatic Networks"],"prefix":"10.3390","volume":"19","author":[{"given":"Nariman","family":"Nabil","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 12566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-8334","authenticated-orcid":false,"given":"Hussein","family":"Sabit","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 12566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2138-1378","authenticated-orcid":false,"given":"Jawaher","family":"Almulhim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, King Faisal University, Alahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9793-0970","authenticated-orcid":false,"given":"Borros","family":"Arneth","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Philipps University Marburg, Baldingerstr. 1, 35043 Marburg, Germany"},{"name":"Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Justus Liebig University Giessen, Feulgenstr 12, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-2000","authenticated-orcid":false,"given":"Shaimaa","family":"Abdel-Ghany","sequence":"additional","affiliation":[{"name":"Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 12566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.21873\/anticanres.17036","article-title":"Harnessing Micronutrient Power: Vitamins, Antioxidants and Probiotics in Breast Cancer Prevention","volume":"44","author":"Mokbel","year":"2024","journal-title":"Anticancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Orrantia-Borunda, E., Anchondo-Nu\u00f1ez, P., Acu\u00f1a-Aguilar, L.E., G\u00f3mez-Valles, F.O., and Ram\u00edrez-Valdespino, C.A. (2022). 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