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In the search for more effective therapeutic options, metal-based complexes are being investigated for their anticancer properties. Cisplatin was the first clinically approved platinum-based drug and, based on its success, other metals (e.g., gold) are being used to design novel compounds. Methods: the antimelanoma potential of a new organometallic cyclometalated Au(III) complex [[Au(CNOxN)Cl2] (CNOxN = 2-(phenyl-(2-pyridinylmethylene)aminoxy acetic acid))] (ST004) was evaluated in vitro and in vivo. Furthermore, the gold-based complex was incorporated in liposomes to overcome solubility and stability problems, to promote accumulation at melanoma sites and to maximize the therapeutic effect while controlling its reactivity. The antiproliferative activity of ST004 formulations was assessed in murine (B16F10) and human (A375 and MNT-1) melanoma cell lines after 24 and 48 h incubation periods. The proof-of-concept of the antimelanoma properties of ST004 formulations was carried out in subcutaneous and metastatic murine melanoma models. Results: the developed liposomal formulations showed a low mean size (around 100 nm), high homogeneity (with a low polydispersity index) and high incorporation efficiency (51 \u00b1 15%). ST004 formulations exhibited antiproliferative activity with EC50 values in the \u03bcmolar range being cell-line- and incubation-period-dependent. On the opposite side, the benchmark antimelanoma compound, dacarbazine (DTIC), presented an EC50 &gt; 100 \u03bcM. Cell cycle analysis revealed an arrest in G0\/G1 phase for Free-ST004 in all cell lines. In turn, LIP-ST004 led to a G0\/G1 halt in B16F10, and to an arrest in S phase in A375 and MNT-1 cells. Preliminary mechanistic studies in human red blood cells suggest that gold-based inhibition of glycerol permeation acts through aquaglyceroporin 3 (AQP3). In a metastatic murine melanoma, a significant reduction in lung metastases in animals receiving LIP-ST004, compared to free gold complex and DTIC, was observed. Conclusion: This study highlights the antimelanoma potential of a new gold-based complex. Additional studies, namely in vivo biodistribution profile and therapeutic validation of this organogold complex in other melanoma models, are expected to be performed in further investigations.<\/jats:p>","DOI":"10.3390\/pharmaceutics16121566","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T09:55:20Z","timestamp":1733478920000},"page":"1566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Liposomal Formulation of an Organogold Complex Enhancing Its Activity as Antimelanoma Agent\u2014In Vitro and In Vivo Studies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7725-4701","authenticated-orcid":false,"given":"Jacinta O.","family":"Pinho","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8168-7267","authenticated-orcid":false,"given":"Mariana","family":"Coelho","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2356-1105","authenticated-orcid":false,"given":"Catarina","family":"Pimp\u00e3o","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"given":"Jahnobi","family":"Konwar","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Jagiellonian University Medical College, 31-008 Krakow, Poland"}]},{"given":"Ana","family":"Godinho-Santos","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8227-4950","authenticated-orcid":false,"given":"Rute M.","family":"Noiva","sequence":"additional","affiliation":[{"name":"CIISA, Interdisciplinary Centre of Research in Animal Health, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, Av. da Universidade T\u00e9cnica, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-430X","authenticated-orcid":false,"given":"Sophie R.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Natural Sciences, Technical University of Munich, 85747 Garching bei M\u00fcnchen, Germany"},{"name":"Faculty of Chemistry, Department of Inorganic Chemistry, University of Vienna, W\u00e4hringer Stra\u00dfe 42, A-1090 Wien, Austria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1599-9542","authenticated-orcid":false,"given":"Angela","family":"Casini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Natural Sciences, Technical University of Munich, 85747 Garching bei M\u00fcnchen, Germany"}]},{"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, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6814-7226","authenticated-orcid":false,"given":"Maria Manuela","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"IBEB\u2014Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"ref_1","unstructured":"WHO (2024, September 15). 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