Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin Cancer

Melanoma is a serious and aggressive type of skin cancer with growing incidence, and it is the leading cause of death among those affected by this disease. Although surgical resection has been employed as a first-line treatment for the early stages of the tumor, noninvasive topical treatments might...

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Main Authors: Fernanda V. Cabral, Bianca de Melo Santana, Camila N. Lange, Bruno L. Batista, Amedea B. Seabra, Martha S. Ribeiro
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/7/1971
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author Fernanda V. Cabral
Bianca de Melo Santana
Camila N. Lange
Bruno L. Batista
Amedea B. Seabra
Martha S. Ribeiro
author_facet Fernanda V. Cabral
Bianca de Melo Santana
Camila N. Lange
Bruno L. Batista
Amedea B. Seabra
Martha S. Ribeiro
author_sort Fernanda V. Cabral
collection DOAJ
description Melanoma is a serious and aggressive type of skin cancer with growing incidence, and it is the leading cause of death among those affected by this disease. Although surgical resection has been employed as a first-line treatment for the early stages of the tumor, noninvasive topical treatments might represent an alternative option. However, they can be irritating to the skin and result in undesirable side effects. In this context, the potential of topical polymeric hydrogels has been investigated for biomedical applications to overcome current limitations. Due to their biocompatible properties, hydrogels have been considered ideal candidates to improve local therapy and promote wound repair. Moreover, drug combinations incorporated into the polymeric-based matrix have emerged as a promising approach to improve the efficacy of cancer therapy, making them suitable vehicles for drug delivery. In this work, we demonstrate the synthesis and characterization of Pluronic F-127 hydrogels (PL) containing the nitric oxide donor S-nitrosoglutathione (GSNO) and copper oxide nanoparticles (CuO NPs) against melanoma cells. Individually applied NO donor or metallic oxide nanoparticles have been widely explored against various types of cancer with encouraging results. This is the first report to assess the potential and possible underlying mechanisms of action of PL containing both NO donor and CuO NPs toward cancer cells. We found that PL + GSNO + CuO NPs significantly reduced cell viability and greatly increased the levels of reactive oxygen species. In addition, this novel platform had a huge impact on different organelles, thus triggering cell death by inducing nuclear changes, a loss of mitochondrial membrane potential, and lipid peroxidation. Thus, GSNO and CuO NPs incorporated into PL hydrogels might find important applications in the treatment of skin cancer.
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spelling doaj.art-dc2b754102b64a90bfc3f40fd59fa6d82023-11-18T20:56:23ZengMDPI AGPharmaceutics1999-49232023-07-01157197110.3390/pharmaceutics15071971Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin CancerFernanda V. Cabral0Bianca de Melo Santana1Camila N. Lange2Bruno L. Batista3Amedea B. Seabra4Martha S. Ribeiro5Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN-CNEN), São Paulo 05508-000, SP, BrazilCenter for Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo André 09210-580, SP, BrazilCenter for Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo André 09210-580, SP, BrazilCenter for Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo André 09210-580, SP, BrazilCenter for Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo André 09210-580, SP, BrazilCenter for Lasers and Applications, Nuclear and Energy Research Institute (IPEN-CNEN), São Paulo 05508-000, SP, BrazilMelanoma is a serious and aggressive type of skin cancer with growing incidence, and it is the leading cause of death among those affected by this disease. Although surgical resection has been employed as a first-line treatment for the early stages of the tumor, noninvasive topical treatments might represent an alternative option. However, they can be irritating to the skin and result in undesirable side effects. In this context, the potential of topical polymeric hydrogels has been investigated for biomedical applications to overcome current limitations. Due to their biocompatible properties, hydrogels have been considered ideal candidates to improve local therapy and promote wound repair. Moreover, drug combinations incorporated into the polymeric-based matrix have emerged as a promising approach to improve the efficacy of cancer therapy, making them suitable vehicles for drug delivery. In this work, we demonstrate the synthesis and characterization of Pluronic F-127 hydrogels (PL) containing the nitric oxide donor S-nitrosoglutathione (GSNO) and copper oxide nanoparticles (CuO NPs) against melanoma cells. Individually applied NO donor or metallic oxide nanoparticles have been widely explored against various types of cancer with encouraging results. This is the first report to assess the potential and possible underlying mechanisms of action of PL containing both NO donor and CuO NPs toward cancer cells. We found that PL + GSNO + CuO NPs significantly reduced cell viability and greatly increased the levels of reactive oxygen species. In addition, this novel platform had a huge impact on different organelles, thus triggering cell death by inducing nuclear changes, a loss of mitochondrial membrane potential, and lipid peroxidation. Thus, GSNO and CuO NPs incorporated into PL hydrogels might find important applications in the treatment of skin cancer.https://www.mdpi.com/1999-4923/15/7/1971CuO nanoparticlesdrug deliverymelanomareactive oxygen speciesS-nitrosoglutathione
spellingShingle Fernanda V. Cabral
Bianca de Melo Santana
Camila N. Lange
Bruno L. Batista
Amedea B. Seabra
Martha S. Ribeiro
Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin Cancer
Pharmaceutics
CuO nanoparticles
drug delivery
melanoma
reactive oxygen species
S-nitrosoglutathione
title Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin Cancer
title_full Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin Cancer
title_fullStr Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin Cancer
title_full_unstemmed Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin Cancer
title_short Pluronic F-127 Hydrogels Containing Copper Oxide Nanoparticles and a Nitric Oxide Donor to Treat Skin Cancer
title_sort pluronic f 127 hydrogels containing copper oxide nanoparticles and a nitric oxide donor to treat skin cancer
topic CuO nanoparticles
drug delivery
melanoma
reactive oxygen species
S-nitrosoglutathione
url https://www.mdpi.com/1999-4923/15/7/1971
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