{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:46:08Z","timestamp":1785746768737,"version":"3.56.0"},"reference-count":68,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Melittin (Mel), the principal cytolytic peptide in honeybee venom (BV), has anticancer activity but limited selectivity. This study examined whether adsorption of Mel to Fe3O4 magnetic nanoparticles (MNPs and MNPs-Mel, respectively), alone or combined with magnetic hyperthermia (MH), modifies cytotoxicity and cell-death phenotype in A375 melanoma cells relative to HaCaT keratinocytes. BV, free Mel, and phospholipase A2 (PLA) were first screened by Alamar Blue assay to select dose-matched conditions; MNPs-Mel (50 or 100 \u00b5g\/mL MNPs, equivalent to approximately 3 or 6 \u00b5g\/mL Mel) was then compared with dose-matched free Mel and unfunctionalized MNPs, and the MNP-containing groups were additionally evaluated with MH. Outcomes included metabolic activity, Annexin V\/propidium iodide flow cytometry, transmission electron microscopy (TEM), and clonogenic potential. At the lower dose, MNPs-Mel produced a larger Annexin-positive fraction in A375 than in HaCaT cells (28.30% vs. 11.80%) and a lower viable-cell fraction (71.64% vs. 87.55%); relative to dose-matched free Mel, the A375 response shifted toward early apoptosis. After MNPs-Mel plus MH, too few A375 cells remained for reliable cytometric acquisition, whereas HaCaT populations remained quantifiable and showed 25.56\u201329.45% apoptosis, predominantly late apoptosis. Free PLA produced smaller changes in metabolic activity than BV or Mel at composition-matched concentrations. TEM supported nanoparticle internalization and treatment-associated mitochondrial and lysosomal alterations. These findings suggest that MNP association changes the cellular presentation of low-dose Mel, while MH increases overall treatment intensity but may narrow the separation between malignant and nonmalignant cells.<\/jats:p>","DOI":"10.3390\/ma19153260","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T08:04:59Z","timestamp":1785744299000},"page":"3260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of In Vitro Cytotoxicity of Honeybee Venom Components and Melittin-Functionalized Fe3O4 Nanoparticles on HaCaT Keratinocytes and A375 Melanoma Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"Alex","family":"C\u00e2mpian","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9270-8529","authenticated-orcid":false,"given":"Olga","family":"Sori\u021b\u0103u","sequence":"additional","affiliation":[{"name":"Radiobiology and Tumor Biology Laboratory, The Oncology Institute \u201cProf. Dr. Ion Chiricu\u021b\u0103\u201d, 34\u201336 Republicii St., 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0684-5851","authenticated-orcid":false,"given":"Mara","family":"Muntean","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5398-1445","authenticated-orcid":false,"given":"Cristian","family":"Iacovi\u021b\u0103","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7968-1643","authenticated-orcid":false,"given":"Oana","family":"Baldasici","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute \u201cProf. Dr. Ion Chiricu\u021b\u0103\u201d, 34\u201336 Republicii St., 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7087-1245","authenticated-orcid":false,"given":"Otilia","family":"Andercou","sequence":"additional","affiliation":[{"name":"Radiobiology and Tumor Biology Laboratory, The Oncology Institute \u201cProf. Dr. Ion Chiricu\u021b\u0103\u201d, 34\u201336 Republicii St., 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0898-7626","authenticated-orcid":false,"given":"Adrian","family":"Florea","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","unstructured":"International Agency for Research on Cancer (2024). 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