Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine

Ty Santiago,1 Rebecca Sinnott DeVaux,2 Katarzyna Kurzatkowska,1 Ricardo Espinal,1 Jason I Herschkowitz,2 Maria Hepel1 1Department of Chemistry, State University of New York at Potsdam, Potsdam, 2Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New...

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Autores principales:	Santiago T, DeVaux RS, Kurzatkowska K, Espinal R, Herschkowitz JI, Hepel M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	d drug delivery Raman spectroscopic nanocarrier testing Flow cytometry Controlled drug release Breast cancer cells Gemcitabine Doxorubicin Folate receptor targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a8ec1f95c3ca4395932a7773c25a02cb
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spelling	oai:doaj.org-article:a8ec1f95c3ca4395932a7773c25a02cb2021-12-02T07:13:44ZSurface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine1178-2013https://doaj.org/article/a8ec1f95c3ca4395932a7773c25a02cb2017-10-01T00:00:00Zhttps://www.dovepress.com/surface-enhanced-raman-scattering-investigation-of-targeted-delivery-a-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ty Santiago,1 Rebecca Sinnott DeVaux,2 Katarzyna Kurzatkowska,1 Ricardo Espinal,1 Jason I Herschkowitz,2 Maria Hepel1 1Department of Chemistry, State University of New York at Potsdam, Potsdam, 2Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New York, Rensselaer, NY, USA Abstract: Advanced and metastatic cancer forms are extremely difficult to treat and require high doses of chemotherapeutics, inadvertently affecting also healthy cells. As a result, the observed survival rates are very low. For instance, gemcitabine (GEM), one of the most effective chemotherapeutic drugs used for the treatment of breast and pancreatic cancers, sees only a 20% efficacy in penetrating cancer tissue, resulting in <5% survival rate in pancreatic cancer. Here, we present a method for delivering the drug that offers mitigation of side effects, as well as a targeted delivery and controlled release of the drug, improving its overall efficacy. By modifying the surface of gold nanoparticles (AuNPs) with covalently bonded thiol linkers, we have immobilized GEM on the nanoparticle (NP) through a pH-sensitive amide bond. This bond prevents the drug from being metabolized or acting on tissue at physiological pH 7.4, but breaks, releasing the drug at acidic pH, characteristic of cancer cells. Further functionalization of the NP with folic acid and/or transferrin (TF) offers a targeted delivery, as cancer cells overexpress folate and TF receptors, which can mediate the endocytosis of the NP carrying the drug. Thus, through the modification of AuNPs, we have been able to produce a nanocarrier containing GEM and folate/TF ligands, which is capable of targeted controlled-release delivery of the drug, reducing the side effects of the drug and increasing its efficacy. Here, we demonstrate the pH-dependent GEM release, using an ultrasensitive surface-enhanced Raman scattering spectroscopy to monitor the GEM loading onto the nanocarrier and follow its stimulated release. Further in vitro studies with model triple-negative breast cancer cell line MDA-MB-231 have corroborated the utility of the proposed nanocarrier method allowing the administration of high drug doses to targeted cancer cells. Keywords: Raman spectroscopic nanocarrier testing, flow cytometry, breast cancer cells, doxorubicin, folate receptor targeting, transferrinSantiago TDeVaux RSKurzatkowska KEspinal RHerschkowitz JIHepel MDove Medical Pressarticled drug deliveryRaman spectroscopic nanocarrier testingFlow cytometryControlled drug releaseBreast cancer cellsGemcitabineDoxorubicinFolate receptor targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7763-7776 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	d drug delivery Raman spectroscopic nanocarrier testing Flow cytometry Controlled drug release Breast cancer cells Gemcitabine Doxorubicin Folate receptor targeting Medicine (General) R5-920
spellingShingle	d drug delivery Raman spectroscopic nanocarrier testing Flow cytometry Controlled drug release Breast cancer cells Gemcitabine Doxorubicin Folate receptor targeting Medicine (General) R5-920 Santiago T DeVaux RS Kurzatkowska K Espinal R Herschkowitz JI Hepel M Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine
description	Ty Santiago,1 Rebecca Sinnott DeVaux,2 Katarzyna Kurzatkowska,1 Ricardo Espinal,1 Jason I Herschkowitz,2 Maria Hepel1 1Department of Chemistry, State University of New York at Potsdam, Potsdam, 2Department of Biomedical Sciences, Cancer Research Center, University at Albany, State University of New York, Rensselaer, NY, USA Abstract: Advanced and metastatic cancer forms are extremely difficult to treat and require high doses of chemotherapeutics, inadvertently affecting also healthy cells. As a result, the observed survival rates are very low. For instance, gemcitabine (GEM), one of the most effective chemotherapeutic drugs used for the treatment of breast and pancreatic cancers, sees only a 20% efficacy in penetrating cancer tissue, resulting in <5% survival rate in pancreatic cancer. Here, we present a method for delivering the drug that offers mitigation of side effects, as well as a targeted delivery and controlled release of the drug, improving its overall efficacy. By modifying the surface of gold nanoparticles (AuNPs) with covalently bonded thiol linkers, we have immobilized GEM on the nanoparticle (NP) through a pH-sensitive amide bond. This bond prevents the drug from being metabolized or acting on tissue at physiological pH 7.4, but breaks, releasing the drug at acidic pH, characteristic of cancer cells. Further functionalization of the NP with folic acid and/or transferrin (TF) offers a targeted delivery, as cancer cells overexpress folate and TF receptors, which can mediate the endocytosis of the NP carrying the drug. Thus, through the modification of AuNPs, we have been able to produce a nanocarrier containing GEM and folate/TF ligands, which is capable of targeted controlled-release delivery of the drug, reducing the side effects of the drug and increasing its efficacy. Here, we demonstrate the pH-dependent GEM release, using an ultrasensitive surface-enhanced Raman scattering spectroscopy to monitor the GEM loading onto the nanocarrier and follow its stimulated release. Further in vitro studies with model triple-negative breast cancer cell line MDA-MB-231 have corroborated the utility of the proposed nanocarrier method allowing the administration of high drug doses to targeted cancer cells. Keywords: Raman spectroscopic nanocarrier testing, flow cytometry, breast cancer cells, doxorubicin, folate receptor targeting, transferrin
format	article
author	Santiago T DeVaux RS Kurzatkowska K Espinal R Herschkowitz JI Hepel M
author_facet	Santiago T DeVaux RS Kurzatkowska K Espinal R Herschkowitz JI Hepel M
author_sort	Santiago T
title	Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine
title_short	Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine
title_full	Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine
title_fullStr	Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine
title_full_unstemmed	Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine
title_sort	surface-enhanced raman scattering investigation of targeted delivery and controlled release of gemcitabine
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/a8ec1f95c3ca4395932a7773c25a02cb
work_keys_str_mv	AT santiagot surfaceenhancedramanscatteringinvestigationoftargeteddeliveryandcontrolledreleaseofgemcitabine AT devauxrs surfaceenhancedramanscatteringinvestigationoftargeteddeliveryandcontrolledreleaseofgemcitabine AT kurzatkowskak surfaceenhancedramanscatteringinvestigationoftargeteddeliveryandcontrolledreleaseofgemcitabine AT espinalr surfaceenhancedramanscatteringinvestigationoftargeteddeliveryandcontrolledreleaseofgemcitabine AT herschkowitzji surfaceenhancedramanscatteringinvestigationoftargeteddeliveryandcontrolledreleaseofgemcitabine AT hepelm surfaceenhancedramanscatteringinvestigationoftargeteddeliveryandcontrolledreleaseofgemcitabine
_version_	1718399531581702144

Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine

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