Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity
Autor(a) principal: | |
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Data de Publicação: | 2015 |
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/1822/39994 |
Resumo: | The relaxivity displayed by Gd3+ chelates immobilized onto gold nanoparticles is the result of complex interplay between nanoparticle size, water exchange rate and chelate structure. In this work we study the effect of the length of -thioalkyl linkers, anchoring fast water exchanging Gd3+ chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd3+ chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM-1s-1 (30 MHz, 25 ºC) were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles is determined mainly by size. Small nanoparticles (HD= 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD= 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggests that functionalized gold nanoparticles hold great potential for further investigation as MRI Contrast Agents. This study contributes to understand the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd3+ complexes. It is a relevant contribution towards “design rules” for nanostructures functionalized with Gd3+ chelates as Contrast Agents for MRI and multimodal imaging. |
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Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivityStabilityIn vivo MRIGold nanoparticlesGd3+ chelatesContrast AgentsLinkersω-thiol functionalized DO3A-N-(alfa-amido)propionate chelatorsFast water exchangeBiodistributionCiências Naturais::Ciências QuímicasScience & TechnologyThe relaxivity displayed by Gd3+ chelates immobilized onto gold nanoparticles is the result of complex interplay between nanoparticle size, water exchange rate and chelate structure. In this work we study the effect of the length of -thioalkyl linkers, anchoring fast water exchanging Gd3+ chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd3+ chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM-1s-1 (30 MHz, 25 ºC) were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles is determined mainly by size. Small nanoparticles (HD= 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD= 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggests that functionalized gold nanoparticles hold great potential for further investigation as MRI Contrast Agents. This study contributes to understand the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd3+ complexes. It is a relevant contribution towards “design rules” for nanostructures functionalized with Gd3+ chelates as Contrast Agents for MRI and multimodal imaging.This work was financially supported by Fundação para a Ciência e a Tecnologia, Portugal: PhD grant SFRH/BD/63994/2009 to Miguel Ferreira and Sabbatical Grant SFRH/BSAB/1328/2013 to José Martins at Bath University, UK; and Rede Nacional de NMR (REDE/1517/RMN/2005) for the acquisition of the Varian VNMRS 600 NMR spectrometer in Coimbra. T.B.R. was supported by a Marie Curie Fellowship (FP/-PEOPLE-2009-IEF 254380) and an EMBO Fellowship (ALTF 1145-2009). Financial support from Ministerio de Ciencia e Innovación, Spain, projects SAF2011-23622 (S.C.) and CTQ2010-20960-C02-02 (P.L.-L.), and Comunidad de Madrid, Spain, project S2010/BMD-2349 (S.C. and P.L.-L), is also acknowledged. B. Mousavi and L. Helm acknowledge financial support by the Swiss National Science Foundation. This work was carried out in the frame of the COST D38 Action “Metal Based Systems for Molecular Imaging” and COST TD1004 Action “Theranostics Imaging and Therapy”.Royal Society of ChemistryUniversidade do MinhoMartins, J. A. R.Ferreira, Paula M. T.Geraldes, Carlos F. G. C.Helm, LotharPrata, Maria I. M.Rodrigues, Sérgio P. J.Rodrigues, Tiago B.Calle, DanielLópez-Larrubia, PilarCerdan, SebastianMousavi, BibimaryamGonçalves, JanainaFerreira, Miguel F.2015-01-222015-01-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/39994engFerreira, M. F., Gonçalves, J., Mousavi, B., Prata, M. I. M., Rodrigues, S. P. J., Calle, D., . . . Geraldes, C. F. G. C. (2015). Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity. Dalton Transactions, 44(9), 4016-4031. doi: 10.1039/c4dt03210a1477-922610.1039/c4dt03210a25611006info: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:RCAAP2023-07-21T12:44:04Zoai:repositorium.sdum.uminho.pt:1822/39994Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:41:41.481136Repositório 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 |
Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity |
title |
Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity |
spellingShingle |
Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity Martins, J. A. R. Stability In vivo MRI Gold nanoparticles Gd3+ chelates Contrast Agents Linkers ω-thiol functionalized DO3A-N-(alfa-amido)propionate chelators Fast water exchange Biodistribution Ciências Naturais::Ciências Químicas Science & Technology |
title_short |
Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity |
title_full |
Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity |
title_fullStr |
Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity |
title_full_unstemmed |
Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity |
title_sort |
Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity |
author |
Martins, J. A. R. |
author_facet |
Martins, J. A. R. Ferreira, Paula M. T. Geraldes, Carlos F. G. C. Helm, Lothar Prata, Maria I. M. Rodrigues, Sérgio P. J. Rodrigues, Tiago B. Calle, Daniel López-Larrubia, Pilar Cerdan, Sebastian Mousavi, Bibimaryam Gonçalves, Janaina Ferreira, Miguel F. |
author_role |
author |
author2 |
Ferreira, Paula M. T. Geraldes, Carlos F. G. C. Helm, Lothar Prata, Maria I. M. Rodrigues, Sérgio P. J. Rodrigues, Tiago B. Calle, Daniel López-Larrubia, Pilar Cerdan, Sebastian Mousavi, Bibimaryam Gonçalves, Janaina Ferreira, Miguel F. |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Martins, J. A. R. Ferreira, Paula M. T. Geraldes, Carlos F. G. C. Helm, Lothar Prata, Maria I. M. Rodrigues, Sérgio P. J. Rodrigues, Tiago B. Calle, Daniel López-Larrubia, Pilar Cerdan, Sebastian Mousavi, Bibimaryam Gonçalves, Janaina Ferreira, Miguel F. |
dc.subject.por.fl_str_mv |
Stability In vivo MRI Gold nanoparticles Gd3+ chelates Contrast Agents Linkers ω-thiol functionalized DO3A-N-(alfa-amido)propionate chelators Fast water exchange Biodistribution Ciências Naturais::Ciências Químicas Science & Technology |
topic |
Stability In vivo MRI Gold nanoparticles Gd3+ chelates Contrast Agents Linkers ω-thiol functionalized DO3A-N-(alfa-amido)propionate chelators Fast water exchange Biodistribution Ciências Naturais::Ciências Químicas Science & Technology |
description |
The relaxivity displayed by Gd3+ chelates immobilized onto gold nanoparticles is the result of complex interplay between nanoparticle size, water exchange rate and chelate structure. In this work we study the effect of the length of -thioalkyl linkers, anchoring fast water exchanging Gd3+ chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd3+ chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM-1s-1 (30 MHz, 25 ºC) were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles is determined mainly by size. Small nanoparticles (HD= 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD= 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggests that functionalized gold nanoparticles hold great potential for further investigation as MRI Contrast Agents. This study contributes to understand the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd3+ complexes. It is a relevant contribution towards “design rules” for nanostructures functionalized with Gd3+ chelates as Contrast Agents for MRI and multimodal imaging. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-01-22 2015-01-22T00:00:00Z |
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 |
http://hdl.handle.net/1822/39994 |
url |
http://hdl.handle.net/1822/39994 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Ferreira, M. F., Gonçalves, J., Mousavi, B., Prata, M. I. M., Rodrigues, S. P. J., Calle, D., . . . Geraldes, C. F. G. C. (2015). Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: Linker effects on the relaxivity. Dalton Transactions, 44(9), 4016-4031. doi: 10.1039/c4dt03210a 1477-9226 10.1039/c4dt03210a 25611006 |
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 |
Royal Society of Chemistry |
publisher.none.fl_str_mv |
Royal Society of Chemistry |
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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1799132966939525120 |