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Osteoarthritis, a prevalent degenerative joint disease associated with aging, is currently not effectively treated by disease-modifying therapies, posing a consistent health burden on individuals and healthcare systems worldwide. Existing treatments, such as nonsteroidal anti-inflammatory drugs and intra-articular injections, are limited by inadequate local drug concentrations and rapid clearance, often necessitating costly joint replacement. Lipid-based NE composed of biocompatible and biodegradable vitamin E and sphingomyelin, associated with the senolytic peptide NE:TUB1, is able to target senescent cells implicated in OA progression. Improved cellular retention and therapeutic effects of the associated TUB1 peptide, compared to its free form, have been demonstrated, suggesting a significant enhancement in therapeutic potential. The incorporation of MNPs to obtain NE:TUB1-MNP formulations offers the advantage of being traceable in vivo through clinically available imaging technologies, with the potential to enhance targeting capabilities through magnetic guidance. The characterization of NE:TUB1-MNPs involved the assessment of their physical and chemical properties, interaction with cells, cytotoxicity profile, and nanoparticle uptake in vitro using human primary adipose-derived stem cells. NE and NE:TUB1-MNP are shown to be stable, non-toxic, and capable of efficient intracellular uptake. The inclusion of MNPs not only supports cell viability and proliferation but also facilitates medium and long-term product traceability within joints, offering a promising approach for localized treatment. The enhanced anti-senescent role of NE:TUB1-MNP formulations are highlighted, suggesting their potential utility in mitigating OA progression and possibly other degenerative diseases. In conclusion, the study presents a novel therapeutic approach for OA, NE:TUB1-MNPs, leveraging the synergistic effects of peptide-functionalized nanoemulsions and magnetic nanoparticles to improve targeted delivery and therapeutic outcomes. This innovative formulation could pave the way for new treatments for OA and other joint-related conditions, offering significant advancements in regenerative medicine.<\/jats:p>","DOI":"10.3390\/ijms26031292","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:36:32Z","timestamp":1738560992000},"page":"1292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Development and Characterization of Magnetic Nanoemulsion-Based Senolytic Peptides for Osteoarthritis Treatment"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3400-2421","authenticated-orcid":false,"given":"Camelia-Mihaela","family":"Zara-Danceanu","sequence":"first","affiliation":[{"name":"National Institute of Research and Development in Technical Physics, 700050 Iasi, Romania"},{"name":"Transcend Ceter Regional Oncology Institute, 700483 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-8886","authenticated-orcid":false,"given":"Jenifer","family":"Garc\u00eda-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Nano-Oncology and Translational Therapeutics Group, Health Research Institute of Santiago de Compostela (IDIS), Servizo Galego de Sa\u00fade (SERGAS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8455-8380","authenticated-orcid":false,"given":"Dumitru-Daniel","family":"Herea","sequence":"additional","affiliation":[{"name":"National Institute of Research and Development in Technical Physics, 700050 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gherca","sequence":"additional","affiliation":[{"name":"National Institute of Research and Development in Technical Physics, 700050 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"de Francisco Carrera","sequence":"additional","affiliation":[{"name":"Nano-Oncology and Translational Therapeutics Group, Health Research Institute of Santiago de Compostela (IDIS), Servizo Galego de Sa\u00fade (SERGAS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9635-6893","authenticated-orcid":false,"given":"Luminita","family":"Labusca","sequence":"additional","affiliation":[{"name":"National Institute of Research and Development in Technical Physics, 700050 Iasi, Romania"},{"name":"Orthopedics and Trauma Clinic, County Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-1469","authenticated-orcid":false,"given":"Maria","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Nano-Oncology and Translational Therapeutics Group, Health Research Institute of Santiago de Compostela (IDIS), Servizo Galego de Sa\u00fade (SERGAS), 15706 Santiago de Compostela, Spain"},{"name":"Biomedical Research Networking Center on Oncology (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"DIVERSA Technologies S.L., Edificio Emprendia, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16044","DOI":"10.1038\/boneres.2016.44","article-title":"Osteoarthritis: Toward a comprehensive understanding of pathological mechanism","volume":"5","author":"Chen","year":"2017","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100587","DOI":"10.1016\/j.eclinm.2020.100587","article-title":"Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies","volume":"29","author":"Cui","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1002\/art.42089","article-title":"Prevalence Trends of Site-Specific Osteoarthritis From 1990 to 2019: Findings from the Global Burden of Disease Study 2019","volume":"74","author":"Long","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.joca.2021.04.020","article-title":"Epidemiology of osteoarthritis","volume":"30","author":"Allen","year":"2022","journal-title":"Osteoarthr. 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