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Resveratrol (RES) is a natural polyphenol with recognized preventive and therapeutic anti-cancer properties. However, poor RES solubility hampers its bioactivity, thus creating a demand for suitable drug delivery systems to improve it. This work aimed to assess the potential of RES-loaded mesoporous silica nanoparticles (MSNs) for human melanoma treatment. RES was efficiently loaded (efficiency &gt; 93%) onto spheroidal (size~60 nm) MSNs. The encapsulation promoted the amorphization of RES and enhanced the release in vitro compared to non-encapsulated RES. The RES release was pH-dependent and markedly faster at pH 5.2 (acid environment in some tumorous tissues) than at pH 7.4 in both encapsulated and bulk forms. The RES release from loaded MSNs was gradual with time, without a burst effect, and well-described by the Weibull model. In vitro cytotoxicity studies on human A375 and MNT-1 melanoma cellular cultures showed a decrease in the cell viability with increasing concentration of RES-loaded MSNs, indicating the potent action of the released RES in both cell lines. The amelanotic cell line A375 was more sensitive to RES concentration than the melanotic MNT-1 cells.<\/jats:p>","DOI":"10.3390\/ma14061382","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T22:13:10Z","timestamp":1615759990000},"page":"1382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Encapsulation and Enhanced Release of Resveratrol from Mesoporous Silica Nanoparticles for Melanoma Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1265-5744","authenticated-orcid":false,"given":"Diogo","family":"Marinheiro","sequence":"first","affiliation":[{"name":"Department of Chemistry &amp; CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0221-3160","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4159-0444","authenticated-orcid":false,"given":"P\u00e1r\u00e1stu","family":"Oskoei","sequence":"additional","affiliation":[{"name":"Department of Biology &amp; CESAM-Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Helena","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biology &amp; CESAM-Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-8880","authenticated-orcid":false,"given":"Ana","family":"Daniel-da-Silva","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s12035-014-9068-z","article-title":"Prevention of Photocarcinogenesis by Agonists of 5-HT1A and Antagonists of 5-HT2A Receptors","volume":"53","author":"Menezes","year":"2016","journal-title":"Mol. 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