Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study

Detalhes bibliográficos
Autor(a) principal: Camacho, Cláudia
Data de Publicação: 2023
Outros Autores: Maciel, Dina, Tomás, Helena, Rodrigues, João
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.13/5491
Resumo: Cisplatin (cis-diamminedichloroplatinum(II)) is a potent chemotherapeutic agent com monly used to treat cancer. However, its use also leads to serious side effects, such as nephrotoxicity, ototoxicity, and cardiotoxicity, which limit the dose that can be safely administered to patients. To minimize these problems, dendrimers may be used as carriers for cisplatin through the coordination of their terminal functional groups to platinum. Here, cisplatin was conjugated to half-generation anionic PAMAM dendrimers in mono- and bidentate forms, and their biological effects were as sessed in vitro. After preparation and characterization of the metallodendrimers, their cytotoxicity was evaluated against several cancer cell lines (A2780, A2780cisR, MCF-7, and CACO-2 cells) and a non-cancer cell line (BJ cells). The results showed that all the metallodendrimers were cytotoxic and that the cytotoxicity level depended on the cell line and the type of coordination mode (mono- or bidentate). Although, in this study, a correlation between dendrimer generation (number of carried metallic fragments) and cytotoxicity could not be completely established, the monodentate coordina tion form of cisplatin resulted in lower IC50 values, thus revealing a more accessible cisplatin release from the dendritic scaffold. Moreover, most of the metallodendrimers were more potent than the cisplatin, especially for the A2780 and A2780cisR cell lines, which showed higher selectivity than for non-cancer cells (BJ cells). The monodentate G0.5COO(Pt(NH3 )2Cl)8 and G2.5COO(Pt(NH3 )2Cl)32 metallodendrimers, as well as the bidentate G2.5COO(Pt(NH3 )2 )16 metallodendrimer, were even more active towards the cisplatin-resistant cell line (A2780cisR cells) than the correspondent cisplatin sensitive one (A2780 cells). Finally, the effect of the metallodendrimers on the hemolysis of human erythrocytes was neglectable, and metallodendrimers’ interaction with calf thymus DNA seemed to be stronger than that of free cisplatin.
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spelling Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative StudyCisplatinAnionic PAMAM dendrimerMonodentateBidentateAnticancerMetallodendrimer.Faculdade de Ciências Exatas e da EngenhariaCentro de Química da MadeiraCisplatin (cis-diamminedichloroplatinum(II)) is a potent chemotherapeutic agent com monly used to treat cancer. However, its use also leads to serious side effects, such as nephrotoxicity, ototoxicity, and cardiotoxicity, which limit the dose that can be safely administered to patients. To minimize these problems, dendrimers may be used as carriers for cisplatin through the coordination of their terminal functional groups to platinum. Here, cisplatin was conjugated to half-generation anionic PAMAM dendrimers in mono- and bidentate forms, and their biological effects were as sessed in vitro. After preparation and characterization of the metallodendrimers, their cytotoxicity was evaluated against several cancer cell lines (A2780, A2780cisR, MCF-7, and CACO-2 cells) and a non-cancer cell line (BJ cells). The results showed that all the metallodendrimers were cytotoxic and that the cytotoxicity level depended on the cell line and the type of coordination mode (mono- or bidentate). Although, in this study, a correlation between dendrimer generation (number of carried metallic fragments) and cytotoxicity could not be completely established, the monodentate coordina tion form of cisplatin resulted in lower IC50 values, thus revealing a more accessible cisplatin release from the dendritic scaffold. Moreover, most of the metallodendrimers were more potent than the cisplatin, especially for the A2780 and A2780cisR cell lines, which showed higher selectivity than for non-cancer cells (BJ cells). The monodentate G0.5COO(Pt(NH3 )2Cl)8 and G2.5COO(Pt(NH3 )2Cl)32 metallodendrimers, as well as the bidentate G2.5COO(Pt(NH3 )2 )16 metallodendrimer, were even more active towards the cisplatin-resistant cell line (A2780cisR cells) than the correspondent cisplatin sensitive one (A2780 cells). Finally, the effect of the metallodendrimers on the hemolysis of human erythrocytes was neglectable, and metallodendrimers’ interaction with calf thymus DNA seemed to be stronger than that of free cisplatin.MDPIDigitUMaCamacho, CláudiaMaciel, DinaTomás, HelenaRodrigues, João2024-01-26T14:46:39Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.13/5491eng: Camacho, C.; Maciel, D.; Tomás, H.; Rodrigues, J. Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study. Pharmaceutics 2023, 15, 689. https://doi.org/10.3390/ pharmaceutics1502068910.3390/pharmaceutics15020689info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-17T05:58:45Zoai:digituma.uma.pt:10400.13/5491Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:58:27.763817Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
title Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
spellingShingle Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
Camacho, Cláudia
Cisplatin
Anionic PAMAM dendrimer
Monodentate
Bidentate
Anticancer
Metallodendrimer
.
Faculdade de Ciências Exatas e da Engenharia
Centro de Química da Madeira
title_short Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
title_full Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
title_fullStr Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
title_full_unstemmed Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
title_sort Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
author Camacho, Cláudia
author_facet Camacho, Cláudia
Maciel, Dina
Tomás, Helena
Rodrigues, João
author_role author
author2 Maciel, Dina
Tomás, Helena
Rodrigues, João
author2_role author
author
author
dc.contributor.none.fl_str_mv DigitUMa
dc.contributor.author.fl_str_mv Camacho, Cláudia
Maciel, Dina
Tomás, Helena
Rodrigues, João
dc.subject.por.fl_str_mv Cisplatin
Anionic PAMAM dendrimer
Monodentate
Bidentate
Anticancer
Metallodendrimer
.
Faculdade de Ciências Exatas e da Engenharia
Centro de Química da Madeira
topic Cisplatin
Anionic PAMAM dendrimer
Monodentate
Bidentate
Anticancer
Metallodendrimer
.
Faculdade de Ciências Exatas e da Engenharia
Centro de Química da Madeira
description Cisplatin (cis-diamminedichloroplatinum(II)) is a potent chemotherapeutic agent com monly used to treat cancer. However, its use also leads to serious side effects, such as nephrotoxicity, ototoxicity, and cardiotoxicity, which limit the dose that can be safely administered to patients. To minimize these problems, dendrimers may be used as carriers for cisplatin through the coordination of their terminal functional groups to platinum. Here, cisplatin was conjugated to half-generation anionic PAMAM dendrimers in mono- and bidentate forms, and their biological effects were as sessed in vitro. After preparation and characterization of the metallodendrimers, their cytotoxicity was evaluated against several cancer cell lines (A2780, A2780cisR, MCF-7, and CACO-2 cells) and a non-cancer cell line (BJ cells). The results showed that all the metallodendrimers were cytotoxic and that the cytotoxicity level depended on the cell line and the type of coordination mode (mono- or bidentate). Although, in this study, a correlation between dendrimer generation (number of carried metallic fragments) and cytotoxicity could not be completely established, the monodentate coordina tion form of cisplatin resulted in lower IC50 values, thus revealing a more accessible cisplatin release from the dendritic scaffold. Moreover, most of the metallodendrimers were more potent than the cisplatin, especially for the A2780 and A2780cisR cell lines, which showed higher selectivity than for non-cancer cells (BJ cells). The monodentate G0.5COO(Pt(NH3 )2Cl)8 and G2.5COO(Pt(NH3 )2Cl)32 metallodendrimers, as well as the bidentate G2.5COO(Pt(NH3 )2 )16 metallodendrimer, were even more active towards the cisplatin-resistant cell line (A2780cisR cells) than the correspondent cisplatin sensitive one (A2780 cells). Finally, the effect of the metallodendrimers on the hemolysis of human erythrocytes was neglectable, and metallodendrimers’ interaction with calf thymus DNA seemed to be stronger than that of free cisplatin.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-01T00:00:00Z
2024-01-26T14:46:39Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.13/5491
url http://hdl.handle.net/10400.13/5491
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv : Camacho, C.; Maciel, D.; Tomás, H.; Rodrigues, J. Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study. Pharmaceutics 2023, 15, 689. https://doi.org/10.3390/ pharmaceutics15020689
10.3390/pharmaceutics15020689
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv MDPI
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