Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy

Przemysław M Jurek,* Konrad Zabłocki,* Urszula Waśko, Maciej P Mazurek, Jacek Otlewski, Filip Jeleń Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Poland *These authors contributed equally to this work Abstract: Compounds that recognize and strongly bind to mo...

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Autores principales: Jurek PM, Zabłocki K, Waśko U, Mazurek MP, Otlewski J, Jeleń F
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:cdf25e99ec414be5bbe368454e6f58a42021-12-02T02:04:23ZAnti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy1178-2013https://doaj.org/article/cdf25e99ec414be5bbe368454e6f58a42017-04-01T00:00:00Zhttps://www.dovepress.com/anti-fgfr1-aptamer-tagged-superparamagnetic-conjugates-for-anticancer--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Przemysław M Jurek,* Konrad Zabłocki,* Urszula Waśko, Maciej P Mazurek, Jacek Otlewski, Filip Jeleń Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Poland *These authors contributed equally to this work Abstract: Compounds that recognize and strongly bind to molecular targets are one of the cornerstones of modern pharmaceutics. Work has been ongoing for the past 25 years on the therapeutic use of aptamers, nucleic acid molecules, whose three-dimensional structure is the result of interactions between complementary base pairs. The aptamers selection methods allow the oligonucleotides which bind the molecular target in its native environment to be quickly isolated from a large library of random oligonucleotides. The possibilities presented for aptamers in the field of targeted therapy require the application of effective carriers to counter the renal clearance effect and/or functional cargo to exert therapeutic action if the aptamer is only used as a targeting moiety. Lately, a material gaining ground in biomedical research is iron oxide particles, which exhibit a superparamagnetic characteristic at nanoscale levels. This allows the iron oxide nanoparticles to convert external magnetic energy into heat, a mechanism known as hyperthermy, and efficiently supports conventional oncological treatment. In this study, we describe an experimentally confirmed functional model of targeted anticancer hyperthermia therapy. Using the systematic evolution of ligands by exponential enrichment technique, we selected a DNA aptamer that specifically binds to the extracellular domain of recombinant fibroblast growth factor receptor type-1 (FGFR1) with a nanomolar dissociation constant. The chosen target plays an important role in many crucial cellular processes and is also considered a candidate protein that is involved in tumor initiation, survival and progression. Next, we combined the selected aptamer with iron oxide nanoparticles to produce aptamer superparamagnetic conjugates (ASCs). Finally, we found that targeted ASCs selectively destroy FGFR1-overexpressing human osteosarcoma cells U2OS upon magnetic field irradiation. Keywords: aptamers, targeted hyperthermia, nanoparticles, iron oxide magnetic nanoparticles, targeted cancer therapyJurek PMZabłocki KWaśko UMazurek MPOtlewski JJeleń FDove Medical Pressarticleaptamerstargeted hyperthermiananoparticlesiron oxide magnetic nanoparticlestargeted cancer therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2941-2950 (2017)
institution DOAJ
collection DOAJ
language EN
topic aptamers
targeted hyperthermia
nanoparticles
iron oxide magnetic nanoparticles
targeted cancer therapy
Medicine (General)
R5-920
spellingShingle aptamers
targeted hyperthermia
nanoparticles
iron oxide magnetic nanoparticles
targeted cancer therapy
Medicine (General)
R5-920
Jurek PM
Zabłocki K
Waśko U
Mazurek MP
Otlewski J
Jeleń F
Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy
description Przemysław M Jurek,* Konrad Zabłocki,* Urszula Waśko, Maciej P Mazurek, Jacek Otlewski, Filip Jeleń Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Poland *These authors contributed equally to this work Abstract: Compounds that recognize and strongly bind to molecular targets are one of the cornerstones of modern pharmaceutics. Work has been ongoing for the past 25 years on the therapeutic use of aptamers, nucleic acid molecules, whose three-dimensional structure is the result of interactions between complementary base pairs. The aptamers selection methods allow the oligonucleotides which bind the molecular target in its native environment to be quickly isolated from a large library of random oligonucleotides. The possibilities presented for aptamers in the field of targeted therapy require the application of effective carriers to counter the renal clearance effect and/or functional cargo to exert therapeutic action if the aptamer is only used as a targeting moiety. Lately, a material gaining ground in biomedical research is iron oxide particles, which exhibit a superparamagnetic characteristic at nanoscale levels. This allows the iron oxide nanoparticles to convert external magnetic energy into heat, a mechanism known as hyperthermy, and efficiently supports conventional oncological treatment. In this study, we describe an experimentally confirmed functional model of targeted anticancer hyperthermia therapy. Using the systematic evolution of ligands by exponential enrichment technique, we selected a DNA aptamer that specifically binds to the extracellular domain of recombinant fibroblast growth factor receptor type-1 (FGFR1) with a nanomolar dissociation constant. The chosen target plays an important role in many crucial cellular processes and is also considered a candidate protein that is involved in tumor initiation, survival and progression. Next, we combined the selected aptamer with iron oxide nanoparticles to produce aptamer superparamagnetic conjugates (ASCs). Finally, we found that targeted ASCs selectively destroy FGFR1-overexpressing human osteosarcoma cells U2OS upon magnetic field irradiation. Keywords: aptamers, targeted hyperthermia, nanoparticles, iron oxide magnetic nanoparticles, targeted cancer therapy
format article
author Jurek PM
Zabłocki K
Waśko U
Mazurek MP
Otlewski J
Jeleń F
author_facet Jurek PM
Zabłocki K
Waśko U
Mazurek MP
Otlewski J
Jeleń F
author_sort Jurek PM
title Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy
title_short Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy
title_full Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy
title_fullStr Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy
title_full_unstemmed Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy
title_sort anti-fgfr1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/cdf25e99ec414be5bbe368454e6f58a4
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