{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:17:42Z","timestamp":1792793862349,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/objective: Osimertinib, an EGFR-targeted agent approved for metastatic NSCLC, shows promise for triple-negative breast cancer due to EGFR overexpression in aggressive tumors. However, oral administration limits tumor delivery and causes systemic side effects. This study aimed to develop chitosan-coated PLGA nanoparticles loaded with osimertinib (CH-P-NPs) to enhance its anticancer efficacy in breast cancer cell lines (MDA-MB-231, MCF-7) by promoting apoptosis and reducing migration in vitro. Methods: CH-P-NPs were synthesized via single-emulsion solvent evaporation and characterized for particle size, zeta potential, encapsulation efficiency, and in vitro release. Anticancer activity was evaluated in MDA-MB-231 and MCF-7 cell lines through in vitro cellular uptake, cytotoxicity, apoptosis induction, and migration inhibition assays. Results: CH-P-NPs exhibited a particle size less than 200 nm, high encapsulation efficiency and a positive zeta potential. Moreover, sustained drug release was achieved with 59.62 \u00b1 1.9% at 24 h. In vitro anticancer studies demonstrated that osimertinib and its nanoparticle formulations showed concentration-dependent cytotoxicity in MDA-MB-231 and MCF-7 cells. CH-P-NPs enhanced cytotoxicity compared with uncoated PLGA nanoparticles (IC50: 1.56 vs. 6 \u00b5g\/mL). CH-P-NPs enhanced cellular uptake in MDA-MB-231 cells, whereas its effect on MCF-7 cellular uptake was cell line-dependent. Annexin V\/PI assay showed that CH-P-NPs significantly enhanced apoptosis compared to free osimertinib in both cell lines. In MDA-MB-231 cells, CH-P-NPs induced ~52.5% total apoptosis versus 3.3% with free drug. In MCF-7 cells, CH-P-NPs induced ~16.6% apoptosis versus 1.5% with free drug. Late apoptosis predominated, indicating irreversible cell death. Wound healing assay showed that CH-P-NPs significantly inhibited migration in both cell lines compared to free osimertinib and control. In MDA-MB-231 cells, CH-P-NPs exhibited greater inhibition at 48 and 72 h, while free osimertinib showed minimal effect. In MCF-7 cells, CH-P-NPs reduced migration at all time points. Conclusions: CH-P-NPs markedly enhanced osimertinib\u2019s anticancer activity by improving cellular uptake, cytotoxicity, inducing apoptosis, and inhibiting migration. This nanoformulation offers a promising strategy to boost efficacy and reduce systemic toxicity in breast cancer treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091179","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EGFR-Targeted Nanoparticle Delivery of Osimertinib for Triple-Negative and Metastatic Breast Cancer Therapy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-1283","authenticated-orcid":false,"given":"Iman M.","family":"Alfagih","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8343-5444","authenticated-orcid":false,"given":"Maryam","family":"Alfagih","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-6279","authenticated-orcid":false,"given":"Alanood","family":"Almurshedi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-2510","authenticated-orcid":false,"given":"Basmah","family":"Aldosari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-0586","authenticated-orcid":false,"given":"Bushra","family":"Alquadeib","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Baraa","family":"Hajjar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7800-8807","authenticated-orcid":false,"given":"Shahad","family":"Almogheerah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rund","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"You, K.S., Yi, Y.W., Cho, J., Park, J.S., and Seong, Y.S. (2021). Potentiating therapeutic effects of epidermal growth factor receptor inhibition in triple-negative breast cancer. Pharmaceuticals, 14.","DOI":"10.3390\/ph14060589"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13058-020-01296-5","article-title":"Triple-negative breast cancer molecular subtyping and treatment progress","volume":"22","author":"Yin","year":"2020","journal-title":"Breast Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chaudhuri, A., Kumar, D.N., Dehari, D., Singh, S., Kumar, P., Bolla, P.K., Kumar, D., and Agrawal, A.K. (2022). Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC). Pharmaceuticals, 15.","DOI":"10.3390\/ph15050542"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1634\/theoncologist.2017-0425","article-title":"FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation","volume":"23","author":"Odogwu","year":"2018","journal-title":"Oncologist"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Veccia, A., Dipasquale, M., Lorenzi, M., Monteverdi, S., Kinspergher, S., Zambotti, E., and Caffo, O. (2025). Osimertinib in the Treatment of Epidermal Growth Factor Receptor-Mutant Early and Locally Advanced Stages of Non-Small-Cell Lung Cancer: Current Evidence and Future Perspectives. Cancers, 17.","DOI":"10.3390\/cancers17040668"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"24549","DOI":"10.3390\/ijms141224549","article-title":"EGFR Mutations in Surgically Resected Fresh Specimens from 697 Consecutive Chinese Patients with Non-Small Cell Lung Cancer and Their Relationships with Clinical Features","volume":"14","author":"Lai","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s40265-018-0916-4","article-title":"Targeting EGFR in Lung Cancer: Current Standards and Developments","volume":"78","author":"Gella","year":"2018","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/onco.13634","article-title":"Adjuvant Osimertinib: A New Standard of Care","volume":"26","author":"Jelinek","year":"2021","journal-title":"Oncologist"},{"key":"ref_9","first-page":"137","article-title":"EGFR targeted therapy in lung cancer; an evolving story","volume":"20","author":"Bartholomew","year":"2017","journal-title":"Respir. Med. Case Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103445","DOI":"10.1016\/j.jddst.2022.103445","article-title":"Paclitaxel and Lapatinib dual loaded chitosan-coated PLGA nanoparticles enhance cytotoxicity by circumventing MDR1-mediated trastuzumab resistance in HER2 positive breast cancers: In-vitro and in-vivo studies","volume":"73","author":"Pitchika","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Anwer, M.K., Ali, E.A., Iqbal, M., Ahmed, M.M., Aldawsari, M.F., Saqr, A.A., Alalaiwe, A., and Soliman, G.A. (2022). Development of Chitosan-Coated PLGA-Based Nanoparticles for Improved Oral Olaparib Delivery: In Vitro Characterization, and In Vivo Pharmacokinetic Studies. Processes, 10.","DOI":"10.3390\/pr10071329"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s12668-020-00797-z","article-title":"Novel Silibinin Loaded Chitosan-Coated PLGA\/PCL Nanoparticles Based Inhalation Formulations with Improved Cytotoxicity and Bioavailability for Lung Cancer","volume":"11","author":"Raval","year":"2021","journal-title":"Bionanoscience"},{"key":"ref_13","first-page":"376","article-title":"A fast, sensitive and greener stability-indicating HPLC method for the quantitative determination of osimertinib","volume":"1","author":"Alhabardi","year":"2025","journal-title":"Acta Chromatogr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12590","DOI":"10.1021\/acsnano.2c04159","article-title":"An Osimertinib-Perfluorocarbon Nanoemulsion with Excellent Targeted Therapeutic Efficacy in Non-small Cell Lung Cancer: Achieving Intratracheal and Intravenous Administration","volume":"16","author":"Yang","year":"2022","journal-title":"ACS Nano"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.ijbiomac.2020.06.154","article-title":"Chitooligosaccharides-modified PLGA nanoparticles enhance the antitumor efficacy of AZD9291 (Osimertinib) by promoting apoptosis","volume":"162","author":"Hu","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1007\/s13346-021-01088-0","article-title":"Pulmonary delivery of osimertinib liposomes for non-small cell lung cancer treatment: Formulation development and in vitro evaluation","volume":"12","author":"Sawant","year":"2022","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2147\/IJN.S337093","article-title":"Chitosan-Coated-PLGA Nanoparticles Enhance the Antitumor and Antimigration Activity of Stattic\u2014A STAT3 Dimerization Blocker","volume":"17","author":"Fong","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Alshehri, S., Imam, S.S., Rizwanullah, M., Fakhri, K.U., Rizvi, M.M., Mahdi, W., and Kazi, M. (2021). Effect of Chitosan Coating on PLGA Nanoparticles for Oral Delivery of Thymoquinone: In Vitro, Ex Vivo, and Cancer Cell Line Assessments. Coatings, 11.","DOI":"10.3390\/coatings11010006"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2174\/187221112802652633","article-title":"Single emulsion-solvent evaporation technique and modifications for the preparation of pharmaceutical polymeric nanoparticles","volume":"6","year":"2012","journal-title":"Recent Pat. Drug Deliv. Formul."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1021\/acsanm.3c06161","article-title":"Chitosan-Coated Poly(lactic-co-glycolic acid) Nanoparticles Loaded with Ursolic Acid for Breast Cancer TherapY","volume":"7","author":"Payomhom","year":"2024","journal-title":"ACS Appl. Nano Mater."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103036","DOI":"10.1016\/j.jddst.2021.103036","article-title":"Chitosan-coated poly (lactic-co-glycolide) nanoparticles for dual delivery of doxorubicin and naringin against MCF-7 cells","volume":"68","author":"Alshememry","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/nbt.3330","article-title":"Principles of nanoparticle design for overcoming biological barriers to drug delivery","volume":"33","author":"Blanco","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"125145","DOI":"10.1016\/j.ijpharm.2024.125145","article-title":"Study on the formation mechanism and effective manipulation of polymorphs and solvates in Osimertinib-Caffeic acid multi-component crystal with distinct properties","volume":"670","author":"Liang","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s13346-020-00802-8","article-title":"Afatinib-loaded inhalable PLGA nanoparticles for localized therapy of non-small cell lung cancer (NSCLC)-development and in-vitro efficacy","volume":"11","author":"Elbatanony","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Alhakamy, N.A., and Shadab, M. (2019). Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120685"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Aibani, N., Rai, R., Patel, P., Cuddihy, G., and Wasan, E.K. (2021). Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101686"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ezzaki, C., Chaari, A., and Al-Othman, A. (2025). Recent Advances on Chitosan-Based Nanoparticles for Brain Drug Delivery. Polymers, 17.","DOI":"10.3390\/polym17223055"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.msec.2019.01.066","article-title":"Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer","volume":"98","author":"Kalyane","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gao, J., Kumari, A., Zeng, X.A., Chan, S., Farooq, M.A., Alee, M., Khan, S.H., Rahaman, A., He, S., and Xin, X. (2023). Coating of chitosan on poly D,L-lactic-co-glycolic acid thymoquinone nanoparticles enhances the anti-tumor activity in triple-negative breast cancer. Front. Chem., 11.","DOI":"10.3389\/fchem.2023.1044953"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00232-012-9516-5","article-title":"Changes in electric properties of human breast cancer cells","volume":"246","author":"Skrzydlewska","year":"2013","journal-title":"J. Membr. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1023\/A:1005986606010","article-title":"Glycosphingolipid composition of MDA-MB-231 and MCF-7 human breast cancer cell lines","volume":"48","author":"Nohara","year":"1998","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100085","DOI":"10.1016\/j.bmt.2025.100085","article-title":"A comprehensive review of cancer drug nanoparticles synthesis, processing technology and its effect in drug delivery","volume":"10","author":"Khan","year":"2025","journal-title":"Biomed. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1039\/C6CS00636A","article-title":"Cellular Uptake of Nanoparticles: Journey Inside the Cell","volume":"46","author":"Behzadi","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"39076","DOI":"10.1021\/acsami.1c10618","article-title":"Uptake of Upconverting Nanoparticles by Breast Cancer Cells: Surface Coating versus the Protein Corona","volume":"13","author":"Voronovic","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/PPO.0000000000000503","article-title":"Triple-negative breast cancer central nervous system metastases from the laboratory to the clinic","volume":"27","author":"Zimmer","year":"2021","journal-title":"Cancer J."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Alfagih, I.M., Almurshedi, A., Aldosari, B., Alquadeib, B., Hajjar, B., Elwali, H., ALtukhaim, H., Alzahrani, E., Alhumaidan, S., and Alharbi, G. (2026). Pulmonary Delivery of Inhalable Sustained Release Nanocomposites Microparticles Encapsulating Osimertinib for Non-Small Cell Lung Cancer Therapy. Pharmaceutics, 18.","DOI":"10.3390\/pharmaceutics18010134"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Moon, H.R., Ospina-Mu\u00f1oz, N., Noe-Kim, V., Yang, Y., Elzey, B.D., Konieczny, S.F., and Han, B. (2020). Subtype-specific characterization of breast cancer invasion using a microfluidic tumor platform. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0234012"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100113","DOI":"10.1016\/j.mbm.2025.100113","article-title":"The underlying difference of metastatic and non-metastatic breast cancer cells in configuring type I collagen fibres to promote migration by cell mechanics","volume":"3","author":"Ouyang","year":"2025","journal-title":"Mechanobiol. Med."},{"key":"ref_39","first-page":"50","article-title":"Disturbing cytoskeleton by engineered nanomaterials for enhanced cancer therapeutics","volume":"29","author":"Xu","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102552","DOI":"10.1016\/j.nantod.2024.102552","article-title":"Breaking biological barriers: Engineering polymeric nanoparticles for cancer therapy","volume":"60","author":"Austria","year":"2025","journal-title":"Nano Today"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:12:17Z","timestamp":1789978337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pharmaceutics18091179"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18091179","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]}}}