Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/141136 |
Resumo: | Funding: The authors thank the financial support from Fundação para a Ciência e Tecnologia (FCT) through projects UIDB/00100/2020, UIDP/00100/2020, UIDB/04138/2020, UIDP/04138/2020, LA/P/0056/2020, and PTDC/QUI-QIN/0586/2020. N. Ribeiro acknowledges FCT for the SFRH/BD/ 135797/2018 grant. Andreia Ferreira acknowledges FCT for the PD/BD/135506/2018 grant. |
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Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer ModelAnimalsAntineoplastic Agents/chemistryColonic Neoplasms/drug therapyCoordination Complexes/chemistryLiposomesMiceZinc/chemistrySDG 3 - Good Health and Well-beingFunding: The authors thank the financial support from Fundação para a Ciência e Tecnologia (FCT) through projects UIDB/00100/2020, UIDP/00100/2020, UIDB/04138/2020, UIDP/04138/2020, LA/P/0056/2020, and PTDC/QUI-QIN/0586/2020. N. Ribeiro acknowledges FCT for the SFRH/BD/ 135797/2018 grant. Andreia Ferreira acknowledges FCT for the PD/BD/135506/2018 grant.Colorectal cancer is the second leading cause of cancer-related mortality. Many current therapies rely on chemotherapeutic agents with poor specificity for tumor cells. The clinical success of cisplatin has prompted the research and design of a huge number of metal-based complexes as potential chemotherapeutic agents. In this study, two zinc(II) complexes, [ZnL 2] and [ZnL(AcO)], where AcO is acetate and L is an organic compound combining 8-hydroxyquinoline and a benzothiazole moiety, were developed and characterized. Analytical and spectroscopic studies, namely, NMR, FTIR, and UV-Vis allowed us to establish the complexes' structures, demonstrating the ligand-binding versatility: tetradentate in [ZnL(AcO)] and bidentate in [ZnL 2]. Complexes were screened in vitro using murine and human colon cancer cells cultured in 2D and 3D settings. In 2D cells, the IC 50 values were <22 µM, while in 3D settings, much higher concentrations were required. [ZnL(AcO)] displayed more suitable antiproliferative properties than [ZnL 2] and was chosen for further studies. Moreover, based on the weak selectivity of the zinc-based complex towards cancer cell lines in comparison to the non-tumorigenic cell line, its incorporation in long-blood-circulating liposomes was performed, aiming to improve its targetability. The resultant optimized liposomal nanoformulation presented an I.E. of 76% with a mean size under 130 nm and a neutral surface charge and released the metal complex in a pH-dependent manner. The antiproliferative properties of [ZnL(AcO)] were maintained after liposomal incorporation. Preliminary safety assays were carried out through hemolytic activity that never surpassed 2% for the free and liposomal forms of [ZnL(AcO)]. Finally, in a syngeneic murine colon cancer mouse model, while free [ZnL(AcO)] was not able to impair tumor progression, the respective liposomal nanoformulation was able to reduce the relative tumor volume in the same manner as the positive control 5-fluorouracil but, most importantly, using a dosage that was 3-fold lower. Overall, our results show that liposomes were able to solve the solubility issues of the new metal-based complex and target it to tumor sites.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)iNOVA4Health - pólo NMSRUNRibeiro, NádiaAlbino, MelissaFerreira, AndreiaEscrevente, CristinaBarral, Duarte CPessoa, João CostaReis, Catarina PintoGaspar, Maria ManuelaCorreia, Isabel2022-06-30T22:25:13Z2022-06-162022-06-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/141136eng1422-0067PURE: 45050819https://doi.org/10.3390/ijms23126728info: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:RCAAP2024-03-11T05:18:25Zoai:run.unl.pt:10362/141136Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:49:55.590194Repositório 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 |
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model |
| title |
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model |
| spellingShingle |
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model Ribeiro, Nádia Animals Antineoplastic Agents/chemistry Colonic Neoplasms/drug therapy Coordination Complexes/chemistry Liposomes Mice Zinc/chemistry SDG 3 - Good Health and Well-being |
| title_short |
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model |
| title_full |
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model |
| title_fullStr |
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model |
| title_full_unstemmed |
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model |
| title_sort |
Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model |
| author |
Ribeiro, Nádia |
| author_facet |
Ribeiro, Nádia Albino, Melissa Ferreira, Andreia Escrevente, Cristina Barral, Duarte C Pessoa, João Costa Reis, Catarina Pinto Gaspar, Maria Manuela Correia, Isabel |
| author_role |
author |
| author2 |
Albino, Melissa Ferreira, Andreia Escrevente, Cristina Barral, Duarte C Pessoa, João Costa Reis, Catarina Pinto Gaspar, Maria Manuela Correia, Isabel |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS RUN |
| dc.contributor.author.fl_str_mv |
Ribeiro, Nádia Albino, Melissa Ferreira, Andreia Escrevente, Cristina Barral, Duarte C Pessoa, João Costa Reis, Catarina Pinto Gaspar, Maria Manuela Correia, Isabel |
| dc.subject.por.fl_str_mv |
Animals Antineoplastic Agents/chemistry Colonic Neoplasms/drug therapy Coordination Complexes/chemistry Liposomes Mice Zinc/chemistry SDG 3 - Good Health and Well-being |
| topic |
Animals Antineoplastic Agents/chemistry Colonic Neoplasms/drug therapy Coordination Complexes/chemistry Liposomes Mice Zinc/chemistry SDG 3 - Good Health and Well-being |
| description |
Funding: The authors thank the financial support from Fundação para a Ciência e Tecnologia (FCT) through projects UIDB/00100/2020, UIDP/00100/2020, UIDB/04138/2020, UIDP/04138/2020, LA/P/0056/2020, and PTDC/QUI-QIN/0586/2020. N. Ribeiro acknowledges FCT for the SFRH/BD/ 135797/2018 grant. Andreia Ferreira acknowledges FCT for the PD/BD/135506/2018 grant. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-06-30T22:25:13Z 2022-06-16 2022-06-16T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/141136 |
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http://hdl.handle.net/10362/141136 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1422-0067 PURE: 45050819 https://doi.org/10.3390/ijms23126728 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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