{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:06:15Z","timestamp":1790784375843,"version":"4.1.0"},"reference-count":118,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T00:00:00Z","timestamp":1637452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa","award":["98337"],"award-info":[{"award-number":["98337"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metastatic melanoma (MM) is a skin malignancy arising from melanocytes, the incidence of which has been rising in recent years. It poses therapeutic challenges due to its resistance to chemotherapeutic drugs and radiation therapy. Photodynamic therapy (PDT) is an alternative non-invasive modality that requires a photosensitizer (PS), specific wavelength of light, and molecular oxygen. Several studies using conventional PSs have highlighted the need for improved PSs for PDT applications to achieve desired therapeutic outcomes. The incorporation of nanoparticles (NPs) and targeting moieties in PDT have appeared as a promising strategy to circumvent various drawbacks associated with non-specific toxicity, poor water solubility, and low bioavailability of the PSs at targeted tissues. Currently, most studies investigating new developments rely on two-dimensional (2-D) monocultures, which fail to accurately mimic tissue complexity. Therefore, three-dimensional (3-D) cell cultures are ideal models to resemble tumor tissue in terms of architectural and functional properties. This review examines various PS drugs, as well as passive and active targeted PS nanoparticle-mediated platforms for PDT treatment of MM on 2-D and 3-D models. The overall findings of this review concluded that very few PDT studies have been conducted within 3-D models using active PS nanoparticle-mediated platforms, and so require further investigation.<\/jats:p>","DOI":"10.3390\/ijms222212549","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T20:58:21Z","timestamp":1637528301000},"page":"12549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Nanoparticle-Based Drug Delivery Systems for Photodynamic Therapy of Metastatic Melanoma: A Review"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3746-707X","authenticated-orcid":false,"given":"Nkune Williams","family":"Nkune","sequence":"first","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5002-827X","authenticated-orcid":false,"given":"Heidi","family":"Abrahamse","sequence":"additional","affiliation":[{"name":"Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,21]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Controlled Drug Delivery Vehicles for Cancer Treatment and Their Performance","volume":"3","author":"Senapati","year":"2018","journal-title":"Signal Transduct. Target. 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