Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma
IntroductionDespite its rarity, cutaneous melanoma (CM) represents the deadliest skin cancer with a high mortality rate, an incidence on the rise, and limited therapeutic options at present. Melanin is a polymeric pigment naturally produced within melanocytes and CM cells that gained a noteworthy at...
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Frontiers Media S.A.
2025-02-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1487854/full |
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| author | Iasmina Marcovici Iasmina Marcovici Raul Chioibas Raul Chioibas Istvan Zupko Iulia Pinzaru Iulia Pinzaru Alina Moaca Alina Moaca Adriana Ledeti Adriana Ledeti Lucian Barbu-Tudoran Lucian Barbu-Tudoran Andreea Geamantan Andreea Geamantan Iasmina Predescu Iasmina Predescu Cristina Adriana Dehelean Cristina Adriana Dehelean |
| author_facet | Iasmina Marcovici Iasmina Marcovici Raul Chioibas Raul Chioibas Istvan Zupko Iulia Pinzaru Iulia Pinzaru Alina Moaca Alina Moaca Adriana Ledeti Adriana Ledeti Lucian Barbu-Tudoran Lucian Barbu-Tudoran Andreea Geamantan Andreea Geamantan Iasmina Predescu Iasmina Predescu Cristina Adriana Dehelean Cristina Adriana Dehelean |
| author_sort | Iasmina Marcovici |
| collection | DOAJ |
| description | IntroductionDespite its rarity, cutaneous melanoma (CM) represents the deadliest skin cancer with a high mortality rate, an incidence on the rise, and limited therapeutic options at present. Melanin is a polymeric pigment naturally produced within melanocytes and CM cells that gained a noteworthy attention due to its pharmacological properties, and potential for the design of nanoplatforms with biomedical applications. Up to date, the utilization of melanin-like nanoparticles (MEL-NPs) in cancer treatment has been well-documented, although their efficacy in CM therapy remains scarcely investigated. The current study presents the preclinical evaluation of MEL-NPs as a potential nanomedicine for CM management.MethodsMEL-NPs were produced through the oxidative polymerization of dopamine and characterized via electron microscopy and UV-VIS spectroscopy. The antioxidant activity was determined by using the DPPH method. The cytotoxic, anti-migratory, anti-clonogenic, pro-oxidant and pro-apoptotic properties of MEL-NPs were investigated in vitro by applying the MTT viability test, bright-field and immunofluorescence microscopy, DCFDA/H2DCFDA test, scratch assay, colony formation assay, and RT-qPCR. The irritant and anti-angiogenic effects were assessed in ovo on the vascularized chorioallantoic membrane (CAM).ResultsThe as-made MEL-NPs presented a spherical morphology, an average size of 85.61 nm, a broad UV-VIS absorption spectrum, and a strong antioxidant activity. After a 24 h treatment, MEL-NPs exerted a selective cytotoxicity in SH-4 and B164A5 CM cells compared to HEMa, HaCaT, and JB6 Cl 41-5a healthy skin cells, except for the concentration of 100 µg/mL, at which their viability declined under 70%. Additionally, MEL-NPs accumulated within the intracellular space of CM cells, forming a perinuclear coating, inhibited their motility and clonogenic potential, increased intracellular oxidative stress, targeted the epithelial-to-mesenchymal transition, and induced apoptosis by altering cell morphology, nuclear aspect, F-actin and tubulin distribution, and by modulating the expression of pro- and anti-apoptotic markers. In ovo, MEL-NPs lacked irritant and vascular toxic effects, while exerting an angio-suppressive activity.ConclusionMEL-NPs demonstrated promising anti-melanoma properties, showing a selective cytotoxicity, a strong anti-invasive effect and a pro-apoptotic activity in CM cells, while inhibiting CAM angiogenesis, these novel findings contributing to future research on the potential application of this nanoplatform in CM therapy. |
| format | Article |
| id | doaj-art-4e8381f769294382805fd9e0d599b3bb |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-4e8381f769294382805fd9e0d599b3bb2025-02-06T07:10:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-02-011610.3389/fphar.2025.14878541487854Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanomaIasmina Marcovici0Iasmina Marcovici1Raul Chioibas2Raul Chioibas3Istvan Zupko4Iulia Pinzaru5Iulia Pinzaru6Alina Moaca7Alina Moaca8Adriana Ledeti9Adriana Ledeti10Lucian Barbu-Tudoran11Lucian Barbu-Tudoran12Andreea Geamantan13Andreea Geamantan14Iasmina Predescu15Iasmina Predescu16Cristina Adriana Dehelean17Cristina Adriana Dehelean18Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaResearch Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaFaculty of Medicine, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaCBS Medcom Hospital, Timisoara, RomaniaFaculty of Pharmacy, University of Szeged, Szeged, HungaryFaculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaResearch Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaFaculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaResearch Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaFaculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaAdvanced Instrumental Screening Center, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Timisoara, RomaniaElectron Microscopy Laboratory “Prof. C. Craciun”, Faculty of Biology and Geology, “Babes-Bolyai” University, Cluj-Napoca, RomaniaElectron Microscopy Integrated Laboratory, National Institute for R and D of Isotopic and Molecular Technologies, Cluj-Napoca, RomaniaFaculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaResearch Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaFaculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaResearch Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaFaculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaResearch Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy from Timisoara, Timisoara, RomaniaIntroductionDespite its rarity, cutaneous melanoma (CM) represents the deadliest skin cancer with a high mortality rate, an incidence on the rise, and limited therapeutic options at present. Melanin is a polymeric pigment naturally produced within melanocytes and CM cells that gained a noteworthy attention due to its pharmacological properties, and potential for the design of nanoplatforms with biomedical applications. Up to date, the utilization of melanin-like nanoparticles (MEL-NPs) in cancer treatment has been well-documented, although their efficacy in CM therapy remains scarcely investigated. The current study presents the preclinical evaluation of MEL-NPs as a potential nanomedicine for CM management.MethodsMEL-NPs were produced through the oxidative polymerization of dopamine and characterized via electron microscopy and UV-VIS spectroscopy. The antioxidant activity was determined by using the DPPH method. The cytotoxic, anti-migratory, anti-clonogenic, pro-oxidant and pro-apoptotic properties of MEL-NPs were investigated in vitro by applying the MTT viability test, bright-field and immunofluorescence microscopy, DCFDA/H2DCFDA test, scratch assay, colony formation assay, and RT-qPCR. The irritant and anti-angiogenic effects were assessed in ovo on the vascularized chorioallantoic membrane (CAM).ResultsThe as-made MEL-NPs presented a spherical morphology, an average size of 85.61 nm, a broad UV-VIS absorption spectrum, and a strong antioxidant activity. After a 24 h treatment, MEL-NPs exerted a selective cytotoxicity in SH-4 and B164A5 CM cells compared to HEMa, HaCaT, and JB6 Cl 41-5a healthy skin cells, except for the concentration of 100 µg/mL, at which their viability declined under 70%. Additionally, MEL-NPs accumulated within the intracellular space of CM cells, forming a perinuclear coating, inhibited their motility and clonogenic potential, increased intracellular oxidative stress, targeted the epithelial-to-mesenchymal transition, and induced apoptosis by altering cell morphology, nuclear aspect, F-actin and tubulin distribution, and by modulating the expression of pro- and anti-apoptotic markers. In ovo, MEL-NPs lacked irritant and vascular toxic effects, while exerting an angio-suppressive activity.ConclusionMEL-NPs demonstrated promising anti-melanoma properties, showing a selective cytotoxicity, a strong anti-invasive effect and a pro-apoptotic activity in CM cells, while inhibiting CAM angiogenesis, these novel findings contributing to future research on the potential application of this nanoplatform in CM therapy.https://www.frontiersin.org/articles/10.3389/fphar.2025.1487854/fullcutaneous melanomamelanin-like nanoparticlescytotoxicitycell migrationepithelial-to-mesenchymal transitionapoptosis |
| spellingShingle | Iasmina Marcovici Iasmina Marcovici Raul Chioibas Raul Chioibas Istvan Zupko Iulia Pinzaru Iulia Pinzaru Alina Moaca Alina Moaca Adriana Ledeti Adriana Ledeti Lucian Barbu-Tudoran Lucian Barbu-Tudoran Andreea Geamantan Andreea Geamantan Iasmina Predescu Iasmina Predescu Cristina Adriana Dehelean Cristina Adriana Dehelean Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma Frontiers in Pharmacology cutaneous melanoma melanin-like nanoparticles cytotoxicity cell migration epithelial-to-mesenchymal transition apoptosis |
| title | Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma |
| title_full | Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma |
| title_fullStr | Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma |
| title_full_unstemmed | Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma |
| title_short | Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma |
| title_sort | preclinical pharmaco toxicological screening of biomimetic melanin like nanoparticles as a potential therapeutic strategy for cutaneous melanoma |
| topic | cutaneous melanoma melanin-like nanoparticles cytotoxicity cell migration epithelial-to-mesenchymal transition apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1487854/full |
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