{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:29:22Z","timestamp":1786364962460,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Program for Research and Technological Innovation Projects","award":["PAPIIT IN216225"],"award-info":[{"award-number":["PAPIIT IN216225"]}]},{"name":"Support Program for Projects to Innovate and Improve Education","award":["PAPIME PE212625"],"award-info":[{"award-number":["PAPIME PE212625"]}]},{"DOI":"10.13039\/501100020417","name":"Research Chair CI2661 and the COMECYT Research Chair","doi-asserted-by":"publisher","award":["CAT2025-0061"],"award-info":[{"award-number":["CAT2025-0061"]}],"id":[{"id":"10.13039\/501100020417","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Resveratrol (RSV) is a phenolic compound that possesses antioxidant properties and whose biological application has been limited by its physicochemical properties, including its low solubility and stability. Methods: In this study, polymeric nanoparticles (NPs) were developed using polylactic acid (PLA) to encapsulate resveratrol and improve its bioavailability, using a factorial design to optimize the formulation and evaluate its cytotoxicity against breast cancer cells. Results: The optimized system presented an average size of 389.2 nm, a PDI of 0.127, a negative z-potential, and an encapsulation efficiency of 76.02%. The statistical analysis indicated that the PLA: RSV ratio was the main determinant of encapsulation percentage and particle size (p &lt; 0.05). On the other hand, with the hemolysis test, blood compatibility was evidenced at all concentrations evaluated, while in the cell assays, the PLA-RSV nanoparticles significantly decreased the cellular viability of MCF-7 and MDA-MB 231 cells compared to untreated cells, and in combination with NP PLA-RSV and doxorubicin, greater cytotoxicity was produced in MCF-7 cells compared to nanoparticle-only treatments (p &lt; 0.05, ANOVA, via followed by a Fisher test). Conclusions: In addition, distinct cytotoxic effects are observed, associated with their tumor phenotype. Taken together, these results suggest that PLA-RSV NPs are a useful system for future studies on redox status and other biological processes important in cancer.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080974","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:38:09Z","timestamp":1786361889000},"page":"974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Characterization of Polylactic Acid-Resveratrol-Based Polymeric Nanoparticles and Their Cytotoxic Effect on Two Breast Cancer Cell Lines in Combination with Doxorubicin"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-3636","authenticated-orcid":false,"given":"Laura Denise","family":"L\u00f3pez Barrera","sequence":"first","affiliation":[{"name":"Laboratorio 9, Toxicolog\u00eda Celular, UIM, Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Km 2.5 Carretera Cuautitl\u00e1n-Teoloyucan, San Sebasti\u00e1n Xhala, Cuautitl\u00e1n Izcalli 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Yair","family":"Santillan Morales","sequence":"additional","affiliation":[{"name":"Laboratorio 9, Toxicolog\u00eda Celular, UIM, Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Km 2.5 Carretera Cuautitl\u00e1n-Teoloyucan, San Sebasti\u00e1n Xhala, Cuautitl\u00e1n Izcalli 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-2367","authenticated-orcid":false,"given":"Joselo Ram\u00f3n","family":"Mart\u00ednez Rosas","sequence":"additional","affiliation":[{"name":"Laboratorio 9, Toxicolog\u00eda Celular, UIM, Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Km 2.5 Carretera Cuautitl\u00e1n-Teoloyucan, San Sebasti\u00e1n Xhala, Cuautitl\u00e1n Izcalli 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8050-1961","authenticated-orcid":false,"given":"Elizabeth","family":"Soria-Castro","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Ch\u00e1vez, Juan Badiano No. 1, Col. Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0900-9162","authenticated-orcid":false,"given":"Patricia","family":"Ram\u00edrez Noguera","sequence":"additional","affiliation":[{"name":"Laboratorio 9, Toxicolog\u00eda Celular, UIM, Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Km 2.5 Carretera Cuautitl\u00e1n-Teoloyucan, San Sebasti\u00e1n Xhala, Cuautitl\u00e1n Izcalli 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-5832","authenticated-orcid":false,"given":"Flora Adriana","family":"Ganem Rondero","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n y Posgrado en Tecnolog\u00eda Farmac\u00e9utica (L-322, Campo 1), Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Cuautitl\u00e1n Izcalli 54740, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1746-806X","authenticated-orcid":false,"given":"Roberto","family":"Diaz-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio 9, Toxicolog\u00eda Celular, UIM, Facultad de Estudios Superiores Cuautitl\u00e1n, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Km 2.5 Carretera Cuautitl\u00e1n-Teoloyucan, San Sebasti\u00e1n Xhala, Cuautitl\u00e1n Izcalli 54714, Estado de M\u00e9xico, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ali, M., Benfante, V., Di Raimondo, D., Salvaggio, G., Tuttolomondo, A., and Comelli, A. (2024). Recent developments in nanoparticle formulations for resveratrol encapsulation as an anticancer agent. Pharmaceuticals, 17.","DOI":"10.3390\/ph17010126"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bohara, R.A., Tabassum, N., Singh, M.P., Gigli, G., Ragusa, A., and Leporatti, S. (2022). Recent overview of resveratrol\u2019s beneficial effects and its nano-delivery systems. Molecules, 27.","DOI":"10.3390\/molecules27165154"},{"key":"ref_4","first-page":"e1353","article-title":"Resveratrol-loaded nanomedicines for cancer applications","volume":"4","author":"Annaji","year":"2021","journal-title":"Cancer Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Elmowafy, M., Shalaby, K., Elkomy, M.H., Alsaidan, O.A., Gomaa, H.A., Abdelgawad, M.A., and Mostafa, E.M. (2023). Polymeric nanoparticles for delivery of natural bioactive agents: Recent advances and challenges. Polymers, 15.","DOI":"10.3390\/polym15051123"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, X., Luo, Q., Zhang, F., Zhao, X., Li, Y., Yang, N., and Feng, L. (2024). Preparation of PLA Nanoparticles and Study of Their Influencing Factors. Molecules, 29.","DOI":"10.3390\/molecules29235566"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Prado-Gotor, R. (2022). New Avenues of Research for Nanoparticle Drug Delivery Systems. Nanomaterials, 12.","DOI":"10.3390\/nano12234141"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41392-019-0068-3","article-title":"Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles","volume":"4","author":"Singh","year":"2019","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Echegaray, N., Berm\u00fadez, R., Nieto, G., Dom\u00ednguez, R., Pateiro, M., Sep\u00falveda, N., Trindade, M.A., and Lorenzo, J.M. (2022). Antioxidant Capacity. Methods to Assess the Quality of Meat Products, Humana Press. Methods and Protocols in Food Science.","DOI":"10.1007\/978-1-0716-2002-1_14"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Barrera, L.D., Diaz-Torres, R., Mart\u00ednez-Rosas, J.R., Salazar, A.M., Rosales, C., and Ram\u00edrez-Noguera, P. (2021). Modification of proliferation and apoptosis in breast cancer cells by exposure of antioxidant nanoparticles due to modulation of the cellular redox state induced by doxorubicin exposure. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13081251"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1039\/c2cs15327k","article-title":"Design of polymeric nanoparticles for biomedical delivery applications","volume":"41","author":"Elsabahy","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27146","DOI":"10.1021\/acsomega.3c02273","article-title":"Effect of nanoparticle weight on the cellular uptake and drug delivery potential of PLGA nanoparticles","volume":"8","author":"Kattel","year":"2023","journal-title":"ACS Omega"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Carreir\u00f3, F., Oliveira, A.M., Neves, A., Pires, B., Nagasamy Venkatesh, D., Durazzo, A., Lucarini, M., Eder, P., Silva, A.M., and Santini, A. (2020). Polymeric nanoparticles: Production, characterization, toxicology and ecotoxicology. Molecules, 25.","DOI":"10.3390\/molecules25163731"},{"key":"ref_14","first-page":"1","article-title":"Advancing Breast Cancer Treatment: The Role of PLA-based Scaffolds in Tumor Microenvironment and Drug Delivery","volume":"8","author":"Pirkani","year":"2024","journal-title":"Multidiscip. Cancer Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9954443","DOI":"10.1155\/2021\/9954443","article-title":"Toxicity of nanoparticles in biomedical application: Nanotoxicology","volume":"2021","author":"Egbuna","year":"2021","journal-title":"J. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1039\/D2NA00290F","article-title":"Tuning the immune system by nanoparticle\u2013biomolecular corona","volume":"4","author":"Palmieri","year":"2022","journal-title":"Nanoscale Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1080\/08941939.2021.1988771","article-title":"Antioxidant effects of resveratrol in intervertebral disk","volume":"35","author":"Huo","year":"2022","journal-title":"J. Investig. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, L., Jin, P., Guan, Y., Luo, M., Wang, Y., He, B., Li, B., He, K., Cao, J., and Huang, C. (2022). Exploiting polyphenol-mediated redox reorientation in cancer therapy. Pharmaceuticals, 15.","DOI":"10.3390\/ph15121540"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6045","DOI":"10.1039\/C5NR00733J","article-title":"Interactions of PLGA nanoparticles with blood components: Protein adsorption. coagulation, activation of the complement system and hemolysis studies","volume":"7","author":"Fornaguera","year":"2015","journal-title":"Nanoscale"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cavalcante de Freitas, P.G., Rodrigues Arruda, B., Ara\u00fajo Mendes, M.G., Barroso de Freitas, J.V., da Silva, M.E., Sampaio, T.L., Petrilli, R., and Eloy, J.O. (2023). Resveratrol-loaded polymeric nanoparticles: The effects of D-\u03b1-Tocopheryl polyethylene glycol 1000 Succinate (TPGS) on Physicochemical and Biological properties against breast Cancer in Vitro and in vivo. Cancers, 15.","DOI":"10.3390\/cancers15102802"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, W., Zhang, L., Chen, T., Guo, W., Bao, X., Wang, D., Ren, B., Wang, H., Li, Y., and Wang, Y. (2017). Anticancer effects of resveratrol-loaded solid lipid nanoparticles on human breast cancer cells. Molecules, 22.","DOI":"10.3390\/molecules22111814"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bao, R., Wang, T., and Jiang, W. (2026). Resveratrol for Cancer Treatment: Effects on Metabolism and Immune Cells. Biomolecules, 16.","DOI":"10.3390\/biom16010118"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s11671-024-03985-y","article-title":"Targeting triple negative breast cancer stem cells using nanocarriers","volume":"19","author":"Dasari","year":"2024","journal-title":"Discov. Nano"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1475-2867-12-47","article-title":"Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer cell line","volume":"12","author":"Osman","year":"2012","journal-title":"Cancer Cell Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.bbagen.2013.10.023","article-title":"Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin","volume":"1840","author":"Kim","year":"2014","journal-title":"Biochim. Biophys. Acta-(Bba)-Gen. Subj."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Talib, W.H., Alsayed, A.R., Farhan, F., and Al Kury, L.T. (2020). Resveratrol and tumor microenvironment: Mechanistic basis and therapeutic targets. Molecules, 25.","DOI":"10.3390\/molecules25184282"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1186\/s12935-021-02280-5","article-title":"Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activation","volume":"21","author":"Alavi","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nchembio.83","article-title":"Identification of RIP1 kinase as a specific cellular target of necrostatins","volume":"4","author":"Degterev","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.cell.2011.11.031","article-title":"Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase","volume":"148","author":"Sun","year":"2012","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.molcel.2011.06.011","article-title":"cIAPs block Ripoptosome formation, a RIP1\/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms","volume":"43","author":"Feoktistova","year":"2011","journal-title":"Mol. 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