FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation

Anna Szlachcic,1 Katarzyna Pala,1 Malgorzata Zakrzewska,1 Piotr Jakimowicz,1 Antoni Wiedlocha,2 Jacek Otlewski11Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Poland; 2Centre for Cancer Biomedicine, Department of Biochemistry, Institute for Cancer Research, The N...

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Autores principales: Szlachcic A, Pala K, Zakrzewska M, Jakimowicz P, Wiedlocha A, Otlewski J
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Lenguaje:EN
Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:da0bcd057f58494da4762120e553c92c2021-12-02T02:17:53ZFGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation1176-91141178-2013https://doaj.org/article/da0bcd057f58494da4762120e553c92c2012-11-01T00:00:00Zhttp://www.dovepress.com/fgf1-gold-nanoparticle-conjugates-targeting-fgfr-efficiently-decrease--a11634https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Anna Szlachcic,1 Katarzyna Pala,1 Malgorzata Zakrzewska,1 Piotr Jakimowicz,1 Antoni Wiedlocha,2 Jacek Otlewski11Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Poland; 2Centre for Cancer Biomedicine, Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayAbstract: Fibroblast growth factor receptors (FGFRs) are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for different types of anticancer therapies. In this study, we designed, constructed, and characterized FGFR-targeted gold nanoconjugates suitable for infrared-induced thermal ablation (localized heating leading to cancer cell death) based on gold nanoparticles (AuNPs). We showed that a recombinant ligand of all FGFRs, human fibroblast growth factor 1 (FGF1), can be used as an agent targeting covalently bound AuNPs to cancer cells overexpressing FGFRs. To assure thermal stability, protease resistance, and prolonged half-life of the targeting protein, we employed highly stable FGF1 variant that retains the biological activities of the wild type FGF1. Novel FGF1 variant, AuNP conjugates are specifically internalized only by the cells expressing FGFRs, and they significantly reduce their viability after irradiation with near-infrared light (down to 40% of control cell viability), whereas the proliferation potential of cells lacking FGFRs is not affected. These results demonstrate the feasibility of FGF1-coated AuNPs for targeted cancer therapy.Keywords: FGF1-conjugates, gold nanoparticles, FGFR-targeted cancer therapy, photothermal therapySzlachcic APala KZakrzewska MJakimowicz PWiedlocha AOtlewski JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5915-5927 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Szlachcic A
Pala K
Zakrzewska M
Jakimowicz P
Wiedlocha A
Otlewski J
FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation
description Anna Szlachcic,1 Katarzyna Pala,1 Malgorzata Zakrzewska,1 Piotr Jakimowicz,1 Antoni Wiedlocha,2 Jacek Otlewski11Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Poland; 2Centre for Cancer Biomedicine, Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayAbstract: Fibroblast growth factor receptors (FGFRs) are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for different types of anticancer therapies. In this study, we designed, constructed, and characterized FGFR-targeted gold nanoconjugates suitable for infrared-induced thermal ablation (localized heating leading to cancer cell death) based on gold nanoparticles (AuNPs). We showed that a recombinant ligand of all FGFRs, human fibroblast growth factor 1 (FGF1), can be used as an agent targeting covalently bound AuNPs to cancer cells overexpressing FGFRs. To assure thermal stability, protease resistance, and prolonged half-life of the targeting protein, we employed highly stable FGF1 variant that retains the biological activities of the wild type FGF1. Novel FGF1 variant, AuNP conjugates are specifically internalized only by the cells expressing FGFRs, and they significantly reduce their viability after irradiation with near-infrared light (down to 40% of control cell viability), whereas the proliferation potential of cells lacking FGFRs is not affected. These results demonstrate the feasibility of FGF1-coated AuNPs for targeted cancer therapy.Keywords: FGF1-conjugates, gold nanoparticles, FGFR-targeted cancer therapy, photothermal therapy
format article
author Szlachcic A
Pala K
Zakrzewska M
Jakimowicz P
Wiedlocha A
Otlewski J
author_facet Szlachcic A
Pala K
Zakrzewska M
Jakimowicz P
Wiedlocha A
Otlewski J
author_sort Szlachcic A
title FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation
title_short FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation
title_full FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation
title_fullStr FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation
title_full_unstemmed FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation
title_sort fgf1-gold nanoparticle conjugates targeting fgfr efficiently decrease cell viability upon nir irradiation
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/da0bcd057f58494da4762120e553c92c
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AT zakrzewskam fgf1goldnanoparticleconjugatestargetingfgfrefficientlydecreasecellviabilityuponnirirradiation
AT jakimowiczp fgf1goldnanoparticleconjugatestargetingfgfrefficientlydecreasecellviabilityuponnirirradiation
AT wiedlochaa fgf1goldnanoparticleconjugatestargetingfgfrefficientlydecreasecellviabilityuponnirirradiation
AT otlewskij fgf1goldnanoparticleconjugatestargetingfgfrefficientlydecreasecellviabilityuponnirirradiation
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