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Nanotechnol."],"accepted":{"date-parts":[[2026,9,30]]},"abstract":"<jats:p>\n                    Breast cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for more effective and less toxic therapeutic strategies. In the present study, a novel nanotherapeutic platform composed of aqueous\n                    <jats:italic>Fritillaria persica L<\/jats:italic>\n                    . (FP) extract and gemcitabine (Gem)-loaded chitosan (CS) nanoparticles (FP\/Gem\/CS-NPs) was successfully developed and evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines. Physicochemical characterization demonstrated the successful fabrication of spherical FP\/Gem\/CS-NPs with a mean hydrodynamic diameter of approximately 69 nm, a polydispersity index (PDI) of 0.500, and a zeta potential of \u221216.2 mV. The nanoparticles demonstrated high entrapment efficiency (78.41%) and sustained drug release behavior, with nearly 50% of Gem released over 72 h, compared with the rapid burst release of free gemcitabine. Biological evaluations revealed that FP\/Gem\/CS-NPs exerted significantly enhanced anticancer activity compared with free Gem or FP extract alone. MTT assays demonstrated strong dose- and time-dependent cytotoxicity, with markedly reduced IC\n                    <jats:sub>50<\/jats:sub>\n                    values in both MCF-7 and MDA-MB-231 cells following nanoparticle treatment. Flow cytometry and caspase-3\/7 analyses confirmed substantial apoptosis induction, particularly in the highly aggressive MDA-MB-231 cells. Gene expression analysis further demonstrated significant upregulation of pro-apoptotic BAX and cell cycle regulator P21, alongside downregulation of anti-apoptotic BCL-2, indicating activation of mitochondrial apoptotic pathways. Moreover, NRF2 expression was elevated, suggesting modulation of oxidative stress responses. Cell cycle analysis revealed prominent G2\/M phase arrest in treated cells. Collectively, these findings indicate that FP\/Gem\/CS-NPs represent a promising synergistic nanotherapeutic system capable of enhancing gemcitabine efficacy while modulating apoptosis, oxidative stress, and cell cycle pathways in breast cancer cells.\n                  <\/jats:p>","DOI":"10.3762\/bjnano.17.96","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:50:30Z","timestamp":1792061430000},"page":"1378-1395","source":"Crossref","is-referenced-by-count":0,"title":["A novel nanoparticle-based co-delivery system of\n                    <i>Fritillaria persica L<\/i>\n                    . extract and gemcitabine for inhibiting breast cancer progression"],"prefix":"10.3762","volume":"17","author":[{"given":"Reyhaneh","family":"Arefimehr","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kzn7k21","id-type":"ROR","asserted-by":"publisher"},{"id":"https:\/\/www.isni.org\/0000000107062472","id-type":"ISNI","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrad","family":"Zibaei Moghadam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negar","family":"Jamshidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7961-7668","authenticated-orcid":false,"given":"Nazanin","family":"Jamshidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2086","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.891824"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21708"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18834"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.2016.1143777"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1159\/000012304"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.55.2984"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.3974"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.3390\/life12030327"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-02004-y"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1021\/mp300370t"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14081589"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113054"},{"key":"ref14","first-page":"854","volume":"7","author":"Serasanambati","year":"2013","journal-title":"Current Trends in Biotechnology and Pharmacy"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1186\/s12896-026-01118-0"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.asej.2023.102424"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020487"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.04.119"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.3390\/polym14050958"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.3390\/coatings11020158"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1080\/00914037.2020.1869737"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e08745"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1007\/s13237-020-00328-x"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2016.03.005"},{"key":"ref25","first-page":"133","volume":"14","author":"Kizil","year":"2014","journal-title":"Propag. 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