{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:24:45Z","timestamp":1775237085211,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT) Portugal","award":["UID\/DTP\/04138\/2019"],"award-info":[{"award-number":["UID\/DTP\/04138\/2019"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT) Portugal","award":["PTDC\/MED-QUI\/31721\/2017"],"award-info":[{"award-number":["PTDC\/MED-QUI\/31721\/2017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT), Portugal","award":["PTDC\/BTM-SAL\/28977\/2017"],"award-info":[{"award-number":["PTDC\/BTM-SAL\/28977\/2017"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT), Portugal","award":["UIDB\/00645\/2020"],"award-info":[{"award-number":["UIDB\/00645\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT), Portugal","award":["UID\/AMB\/50017\/2019"],"award-info":[{"award-number":["UID\/AMB\/50017\/2019"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT), Portugal","award":["SFRH\/BD\/117586\/2016"],"award-info":[{"award-number":["SFRH\/BD\/117586\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Cancer is a major health concern and the prognosis is often poor. Significant advances in nanotechnology are now driving a revolution in cancer detection and treatment. The goal of this study was to develop a novel hybrid nanosystem for melanoma treatment, integrating therapeutic and magnetic targeting modalities. Hence, we designed long circulating and pH-sensitive liposomes loading both dichloro(1,10-phenanthroline) copper (II) (Cuphen), a cytotoxic metallodrug, and iron oxide nanoparticles (IONPs). The synthetized IONPs were characterized by transmission electron microscopy and dynamic light scattering. Lipid-based nanoformulations were prepared by the dehydration rehydration method, followed by an extrusion step for reducing and homogenizing the mean size. Liposomes were characterized in terms of incorporation parameters and mean size. High Cuphen loadings were obtained and the presence of IONPs slightly reduced Cuphen incorporation parameters. Cuphen antiproliferative properties were preserved after association to liposomes and IONPs (at 2 mg\/mL) did not interfere on cellular proliferation of murine and human melanoma cell lines. Moreover, the developed nanoformulations displayed magnetic properties. The absence of hemolytic activity for formulations under study demonstrated their safety for parenteral administration. In conclusion, a lipid-based nanosystem loading the cytotoxic metallodrug, Cuphen, and displaying magnetic properties was successfully designed.<\/jats:p>","DOI":"10.3390\/nano10040693","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T03:58:39Z","timestamp":1586231919000},"page":"693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Novel Hybrid Nanosystem Integrating Cytotoxic and Magnetic Properties as a Tool to Potentiate Melanoma Therapy"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4196-6808","authenticated-orcid":false,"given":"Nuno","family":"Cruz","sequence":"first","affiliation":[{"name":"Instituto de Biof\u00edsica e Engenharia Biom\u00e9dica (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7725-4701","authenticated-orcid":false,"given":"Jacinta Oliveira","family":"Pinho","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8487-110X","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Soveral","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-5912","authenticated-orcid":false,"given":"Lia","family":"Ascens\u00e3o","sequence":"additional","affiliation":[{"name":"Centro de Estudos do Ambiente e do Mar (CESAM), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"given":"Nuno","family":"Matela","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica e Engenharia Biom\u00e9dica (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-4031","authenticated-orcid":false,"given":"Catarina","family":"Reis","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica e Engenharia Biom\u00e9dica (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Maria Manuela","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15003","DOI":"10.1038\/nrdp.2015.3","article-title":"Melanoma","volume":"1","author":"Schadendorf","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","first-page":"134","article-title":"Principles of cancer treatment by chemotherapy","volume":"36","author":"Dickens","year":"2018","journal-title":"Surg"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1200\/JCO.2009.23.4799","article-title":"Final version of 2009 AJCC melanoma staging and classification","volume":"27","author":"Balch","year":"2009","journal-title":"J. Clin. 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