pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance

Detalhes bibliográficos
Autor(a) principal: Teixeira, Patrícia V.
Data de Publicação: 2023
Outros Autores: Adega, Filomena, Martins-Lopes, Paula, Machado, Raul, Lopes, Carla M., Lúcio, M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/1822/85468
Resumo: Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.
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spelling pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performanceCancerChemotherapeutic agentsDoxorubicinDrug-delivery systemsLyotropic non-lamellar liquid crystalline nanoassembliesScience & TechnologyCurrent needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.This research was funded by FCT/MCTES—Foundation for Science and Technology I.P. from the Minister of Science, Technology, and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) by the COMPETE—Programa Operacional Factores de Competitividade (POFC) through the project CONCERT [POCI-01-0145-FEDER-032651 and PTDC/NAN-MAT/326512017]. This work was also supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UIDB/04650/2020 and UIDB/04050/2020 (CF-UM-UP and CBMA). The authors are grateful for the support of the BioISI center grant (UIDB/04046/2020 and UIDP/04046/2020), financed by FCT. R.M. acknowledges FCT I.P. for funding within the Scientific Employment Stimulus instrument (CEECIND/00526/2018).Multidisciplinary Digital Publishing InstituteUniversidade do MinhoTeixeira, Patrícia V.Adega, FilomenaMartins-Lopes, PaulaMachado, RaulLopes, Carla M.Lúcio, M.2023-01-182023-01-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/85468engTeixeira, P.V.; Adega, F.; Martins-Lopes, P.; Machado, R.; Lopes, C.M.; Lúcio, M. pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance. Pharmaceutics 2023, 15, 326. https://doi.org/10.3390/pharmaceutics150203261999-492310.3390/pharmaceutics15020326https://www.mdpi.com/1999-4923/15/2/326info: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:RCAAP2023-07-21T12:32:22Zoai:repositorium.sdum.uminho.pt:1822/85468Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:27:43.174149Repositório 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 pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance
title pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance
spellingShingle pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance
Teixeira, Patrícia V.
Cancer
Chemotherapeutic agents
Doxorubicin
Drug-delivery systems
Lyotropic non-lamellar liquid crystalline nanoassemblies
Science & Technology
title_short pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance
title_full pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance
title_fullStr pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance
title_full_unstemmed pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance
title_sort pH-responsive hybrid nanoassemblies for cancer treatment: formulation development, optimization, and in vitro therapeutic performance
author Teixeira, Patrícia V.
author_facet Teixeira, Patrícia V.
Adega, Filomena
Martins-Lopes, Paula
Machado, Raul
Lopes, Carla M.
Lúcio, M.
author_role author
author2 Adega, Filomena
Martins-Lopes, Paula
Machado, Raul
Lopes, Carla M.
Lúcio, M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Teixeira, Patrícia V.
Adega, Filomena
Martins-Lopes, Paula
Machado, Raul
Lopes, Carla M.
Lúcio, M.
dc.subject.por.fl_str_mv Cancer
Chemotherapeutic agents
Doxorubicin
Drug-delivery systems
Lyotropic non-lamellar liquid crystalline nanoassemblies
Science & Technology
topic Cancer
Chemotherapeutic agents
Doxorubicin
Drug-delivery systems
Lyotropic non-lamellar liquid crystalline nanoassemblies
Science & Technology
description Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.
publishDate 2023
dc.date.none.fl_str_mv 2023-01-18
2023-01-18T00:00:00Z
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 https://hdl.handle.net/1822/85468
url https://hdl.handle.net/1822/85468
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Teixeira, P.V.; Adega, F.; Martins-Lopes, P.; Machado, R.; Lopes, C.M.; Lúcio, M. pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance. Pharmaceutics 2023, 15, 326. https://doi.org/10.3390/pharmaceutics15020326
1999-4923
10.3390/pharmaceutics15020326
https://www.mdpi.com/1999-4923/15/2/326
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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