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Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery

This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sar...

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Autores principales: Skalickova, Sylvie, Loffelmann, Martin, Gargulak, Michael, Kepinska, Marta, Docekalova, Michaela, Uhlirova, Dagmar, Stankova, Martina, Fernandez, Carlos, Milnerowicz, Halina, Ruttkay-Nedecky, Branislav, Kizek, Rene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746925/
https://www.ncbi.nlm.nih.gov/pubmed/29292780
http://dx.doi.org/10.3390/nano7120435
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author Skalickova, Sylvie
Loffelmann, Martin
Gargulak, Michael
Kepinska, Marta
Docekalova, Michaela
Uhlirova, Dagmar
Stankova, Martina
Fernandez, Carlos
Milnerowicz, Halina
Ruttkay-Nedecky, Branislav
Kizek, Rene
author_facet Skalickova, Sylvie
Loffelmann, Martin
Gargulak, Michael
Kepinska, Marta
Docekalova, Michaela
Uhlirova, Dagmar
Stankova, Martina
Fernandez, Carlos
Milnerowicz, Halina
Ruttkay-Nedecky, Branislav
Kizek, Rene
author_sort Skalickova, Sylvie
collection PubMed
description This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sarcosine in the prostate cancer cells. The prostate cancer targeting was mediated by the AntiSar antibodies decorated surface of the nanocage. Formation of the chitosan nanoparticles was determined using a ninhydrin assay and differential pulse voltammetry. Obtained results showed the strong effect of tripolyphosphine on the nanoparticle formation. The zinc ions affected strong chitosan backbone coiling both in inner and outer chitosan nanoparticle structure. Zinc electrochemical signal depended on the level of the complex formation and the potential shift from −960 to −950 mV. Formed complex is suitable for doxorubicin delivery. It was observed the 20% entrapment efficiency of doxorubicin and strong dependence of drug release after 120 min in the blood environment. The functionality of the designed nanotransporter was proven. The purposed determination showed linear dependence in the concentration range of Anti-sarcosine IgG labeled gold nanoparticles from 0 to 1000 µg/mL and the regression equation was found to be y = 3.8x − 66.7 and R(2) = 0.99. Performed ELISA confirmed the ability of Anti-sarcosine IgG labeled chitosan nanoparticles with loaded doxorubicin to bind to the sarcosine molecule. Observed hemolytic activity of the nanotransporter was 40%. Inhibition activity of our proposed nanotransporter was evaluated to be 0% on the experimental model of S. cerevisiae. Anti-sarcosine IgG labeled chitosan nanoparticles, with loaded doxorubicin stabilized by Zn ions, are a perspective type of nanocarrier for targeted drug therapy managed by specific interaction with sarcosine and metallothionein for prostate cancer.
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spelling pubmed-57469252018-01-03 Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery Skalickova, Sylvie Loffelmann, Martin Gargulak, Michael Kepinska, Marta Docekalova, Michaela Uhlirova, Dagmar Stankova, Martina Fernandez, Carlos Milnerowicz, Halina Ruttkay-Nedecky, Branislav Kizek, Rene Nanomaterials (Basel) Article This work investigated the preparation of chitosan nanoparticles used as carriers for doxorubicin for targeted cancer delivery. Prepared nanocarriers were stabilized and functionalized via zinc ions incorporated into the chitosan nanoparticle backbone. We took the advantage of high expression of sarcosine in the prostate cancer cells. The prostate cancer targeting was mediated by the AntiSar antibodies decorated surface of the nanocage. Formation of the chitosan nanoparticles was determined using a ninhydrin assay and differential pulse voltammetry. Obtained results showed the strong effect of tripolyphosphine on the nanoparticle formation. The zinc ions affected strong chitosan backbone coiling both in inner and outer chitosan nanoparticle structure. Zinc electrochemical signal depended on the level of the complex formation and the potential shift from −960 to −950 mV. Formed complex is suitable for doxorubicin delivery. It was observed the 20% entrapment efficiency of doxorubicin and strong dependence of drug release after 120 min in the blood environment. The functionality of the designed nanotransporter was proven. The purposed determination showed linear dependence in the concentration range of Anti-sarcosine IgG labeled gold nanoparticles from 0 to 1000 µg/mL and the regression equation was found to be y = 3.8x − 66.7 and R(2) = 0.99. Performed ELISA confirmed the ability of Anti-sarcosine IgG labeled chitosan nanoparticles with loaded doxorubicin to bind to the sarcosine molecule. Observed hemolytic activity of the nanotransporter was 40%. Inhibition activity of our proposed nanotransporter was evaluated to be 0% on the experimental model of S. cerevisiae. Anti-sarcosine IgG labeled chitosan nanoparticles, with loaded doxorubicin stabilized by Zn ions, are a perspective type of nanocarrier for targeted drug therapy managed by specific interaction with sarcosine and metallothionein for prostate cancer. MDPI 2017-12-08 /pmc/articles/PMC5746925/ /pubmed/29292780 http://dx.doi.org/10.3390/nano7120435 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Skalickova, Sylvie
Loffelmann, Martin
Gargulak, Michael
Kepinska, Marta
Docekalova, Michaela
Uhlirova, Dagmar
Stankova, Martina
Fernandez, Carlos
Milnerowicz, Halina
Ruttkay-Nedecky, Branislav
Kizek, Rene
Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery
title Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery
title_full Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery
title_fullStr Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery
title_full_unstemmed Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery
title_short Zinc-Modified Nanotransporter of Doxorubicin for Targeted Prostate Cancer Delivery
title_sort zinc-modified nanotransporter of doxorubicin for targeted prostate cancer delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746925/
https://www.ncbi.nlm.nih.gov/pubmed/29292780
http://dx.doi.org/10.3390/nano7120435
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