{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:16:29Z","timestamp":1789514189802,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Head and neck squamous cell carcinomas (HNSCCs) are considered the most common histological type of head and neck cancer. This study aims to develop a drug delivery system based on zein protein nanoparticles (Zein NPs) to enhance the therapeutic effect of the anticancer peptide, Pistacia zardin1 (PZ1), for the treatment of maxillofacial cancers. PZ1-Zein NPs were synthesized by the desolvation method. These spherical nanoparticles (size: 162.8 nm, PDI: 0.27) showed high encapsulation efficiency (89%) and pH-responsive release (with higher drug release in the acidic tumor microenvironment). In vitro cytotoxicity assays showed that PZ1-Zein NPs significantly reduced IC50 values in HNSCC cell lines (e.g., SCC-25: 7.5 \u00b5M vs. 19.3 \u00b5M for free peptide, p &lt; 0.001) while exhibiting improved selectivity for cancer cells over normal HaCaT cells. Mechanistic investigations confirmed that PZ1-Zein NPs significantly increased apoptosis, as shown by increased caspase-3\/7 activity (5.8-fold vs. 2.6-fold). These findings highlight PZ1-Zein NPs as a promising nanomedicine strategy and a candidate functional component for future dual-functional scaffolds aimed at targeted hard tissue engineering and surgery in HNSCC management.<\/jats:p>","DOI":"10.3390\/nano16040254","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:11:28Z","timestamp":1771240288000},"page":"254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Treatment of Maxillofacial Cancers by Zein Nanoparticles Loaded with Anticancer Peptide Pistacia Zardin1: Enhanced Cytotoxicity and Apoptosis Induction in Head and Neck Squamous Cell Carcinoma (HNSCC)"],"prefix":"10.3390","volume":"16","author":[{"suffix":"Jr.","given":"Andrej","family":"Jen\u010da","sequence":"first","affiliation":[{"name":"Academy of Ko\u0161ice, Pavol Jozef \u0160af\u00e1rik University, Solmea s.r.o., Ba\u010d\u00edkova 7, 04001 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0590-9489","authenticated-orcid":false,"given":"Elham","family":"Saberian","sequence":"additional","affiliation":[{"name":"Academy of Ko\u0161ice, Pavol Jozef \u0160af\u00e1rik University, Solmea s.r.o., Ba\u010d\u00edkova 7, 04001 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janka","family":"Jen\u010dov\u00e1","sequence":"additional","affiliation":[{"name":"Specialized Hospital Head and Neck Diseases, Academy of Ko\u0161ice, Pavol Jozef \u0160af\u00e1rik University, Solmea s.r.o., Ba\u010d\u00edkova 7, 04001 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1na","family":"Petr\u00e1\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"Academy of Ko\u0161ice, Pavol Jozef \u0160af\u00e1rik University, Solmea s.r.o., Ba\u010d\u00edkova 7, 04001 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4501-7407","authenticated-orcid":false,"given":"Andrej","family":"Jen\u010da","sequence":"additional","affiliation":[{"name":"Academy of Ko\u0161ice, Pavol Jozef \u0160af\u00e1rik University, Solmea s.r.o., Ba\u010d\u00edkova 7, 04001 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-4520","authenticated-orcid":false,"given":"David","family":"Mills","sequence":"additional","affiliation":[{"name":"Molecular Science and Nanotechnology, College of Engineering and Science, Louisiana Tech University, Ruston, LA 71272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1501-2560","authenticated-orcid":false,"given":"Hadi","family":"Zare-Zardini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Meybod University, Meybod 896169557, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli\u0161ka","family":"Kub\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Anatomy, Comenius University, 81108 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3375-7992","authenticated-orcid":false,"given":"Simona","family":"Diani\u0161kov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Slovak Medical University, 81108 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetyana","family":"Pyndus","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Pavol Jozef \u0160af\u00e1rik University, Solmea s.r.o., Ba\u010d\u00edkova 7, 04001 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and neck squamous cell carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. 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