Intracellular trafficking of size-tuned nanoparticles for drug delivery
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/88566 |
Resumo: | Polymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP performance, including drug delivery capabilities and intracellular trafficking. For that, poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG) NPs with sizes of 50 and 70 nm were precisely tailored. To assess their prowess in encapsulating and releasing therapeutic agents, we have employed doxorubicin (Dox), a well-established anticancer drug widely utilized in clinical settings, as a model drug. Then, the beneficial effect of the developed nanoformulations was evaluated in breast cancer cells. Finally, we performed a semiquantitative analysis of both NPsâ uptake and intracellular localization by immunostaining lysosomes, early endosomes, and recycling endosomes. The results show that the smaller NPs (50 nm) were able to reduce the metabolic activity of cancer cells more efficiently than NPs of 70 nm, in a time and concentration-dependent manner. These findings are corroborated by intracellular trafficking studies that reveal an earlier and higher uptake of NPs, with 50 nm compared to the 70 nm ones, by the breast cancer cells. Consequently, this study demonstrates that NP size, even in small increments, has an important impact on their therapeutic effect. |
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Intracellular trafficking of size-tuned nanoparticles for drug deliveryInternalizationIntracellular traffickingPEGylationPolymeric nanoparticlesSize-controlled nanoparticlesPolymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP performance, including drug delivery capabilities and intracellular trafficking. For that, poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG) NPs with sizes of 50 and 70 nm were precisely tailored. To assess their prowess in encapsulating and releasing therapeutic agents, we have employed doxorubicin (Dox), a well-established anticancer drug widely utilized in clinical settings, as a model drug. Then, the beneficial effect of the developed nanoformulations was evaluated in breast cancer cells. Finally, we performed a semiquantitative analysis of both NPsâ uptake and intracellular localization by immunostaining lysosomes, early endosomes, and recycling endosomes. The results show that the smaller NPs (50 nm) were able to reduce the metabolic activity of cancer cells more efficiently than NPs of 70 nm, in a time and concentration-dependent manner. These findings are corroborated by intracellular trafficking studies that reveal an earlier and higher uptake of NPs, with 50 nm compared to the 70 nm ones, by the breast cancer cells. Consequently, this study demonstrates that NP size, even in small increments, has an important impact on their therapeutic effect.The authors would like to thank the funders that allowed for carrying out this work, namely the Fundação para a Ciência e a Tecnologia (FCT) for the S. Gimondi fellowship (PD/BD/143140/2019; COVID/BD/153033/2022) and for the Associated Laboratory Project, ICVS/3B’s (UIDP/50026/2020). This work was also supported by HEALTH UNORTE (NORTE-01-0145-FEDER-000039). The authors would also like to thank the contributions to this research from the project “TERM RES Hub—Scientific Infrastructure for Tissue Engineering and Regenerative Medicine”, reference PINFRA/22190/2016 (Norte-01-0145-FEDER-022190), funded by the Portuguese National Science Foundation (FCT) in cooperation with the Northern Portugal Regional Coordination and Development Commission (CCDR-N), for providing relevant lab facilities, state-of-the-art equipment, and highly qualified human resources.Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoGimondi, SaraFerreira, Helena Susana Costa MachadoReis, R. L.Neves, N. M.2023-122023-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/88566engGimondi S., Ferreira H., Reis R. L., Neves N. M. Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery, International Journal Of Molecular Sciences, Vol. 25, pp. 312, doi:10.3390/ijms25010312, 20231661-65961422-006710.3390/ijms2501031238203483312https://doi.org/10.3390/ijms25010312info: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:RCAAP2024-02-24T01:23:56Zoai:repositorium.sdum.uminho.pt:1822/88566Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:37:16.863874Repositório 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 |
Intracellular trafficking of size-tuned nanoparticles for drug delivery |
title |
Intracellular trafficking of size-tuned nanoparticles for drug delivery |
spellingShingle |
Intracellular trafficking of size-tuned nanoparticles for drug delivery Gimondi, Sara Internalization Intracellular trafficking PEGylation Polymeric nanoparticles Size-controlled nanoparticles |
title_short |
Intracellular trafficking of size-tuned nanoparticles for drug delivery |
title_full |
Intracellular trafficking of size-tuned nanoparticles for drug delivery |
title_fullStr |
Intracellular trafficking of size-tuned nanoparticles for drug delivery |
title_full_unstemmed |
Intracellular trafficking of size-tuned nanoparticles for drug delivery |
title_sort |
Intracellular trafficking of size-tuned nanoparticles for drug delivery |
author |
Gimondi, Sara |
author_facet |
Gimondi, Sara Ferreira, Helena Susana Costa Machado Reis, R. L. Neves, N. M. |
author_role |
author |
author2 |
Ferreira, Helena Susana Costa Machado Reis, R. L. Neves, N. M. |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Gimondi, Sara Ferreira, Helena Susana Costa Machado Reis, R. L. Neves, N. M. |
dc.subject.por.fl_str_mv |
Internalization Intracellular trafficking PEGylation Polymeric nanoparticles Size-controlled nanoparticles |
topic |
Internalization Intracellular trafficking PEGylation Polymeric nanoparticles Size-controlled nanoparticles |
description |
Polymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP performance, including drug delivery capabilities and intracellular trafficking. For that, poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG) NPs with sizes of 50 and 70 nm were precisely tailored. To assess their prowess in encapsulating and releasing therapeutic agents, we have employed doxorubicin (Dox), a well-established anticancer drug widely utilized in clinical settings, as a model drug. Then, the beneficial effect of the developed nanoformulations was evaluated in breast cancer cells. Finally, we performed a semiquantitative analysis of both NPsâ uptake and intracellular localization by immunostaining lysosomes, early endosomes, and recycling endosomes. The results show that the smaller NPs (50 nm) were able to reduce the metabolic activity of cancer cells more efficiently than NPs of 70 nm, in a time and concentration-dependent manner. These findings are corroborated by intracellular trafficking studies that reveal an earlier and higher uptake of NPs, with 50 nm compared to the 70 nm ones, by the breast cancer cells. Consequently, this study demonstrates that NP size, even in small increments, has an important impact on their therapeutic effect. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-12 2023-12-01T00:00:00Z |
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/1822/88566 |
url |
https://hdl.handle.net/1822/88566 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Gimondi S., Ferreira H., Reis R. L., Neves N. M. Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery, International Journal Of Molecular Sciences, Vol. 25, pp. 312, doi:10.3390/ijms25010312, 2023 1661-6596 1422-0067 10.3390/ijms25010312 38203483 312 https://doi.org/10.3390/ijms25010312 |
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 (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
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 |
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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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