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Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells
Nanomaterials are a central pillar in modern medicine. They are thought to optimize drug delivery, enhance therapeutic efficacy, and reduce side-effects. To foster this technology, analytical methods are needed to validate not only the localization and distribution of these nanomaterials, but also t...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397571/ https://www.ncbi.nlm.nih.gov/pubmed/36016563 http://dx.doi.org/10.3389/fphar.2022.962763 |
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author | Tolstik, E. Gongalsky, M. B. Dierks, J. Brand, T. Pernecker, M. Pervushin, N. V. Maksutova, D. E. Gonchar, K. A. Samsonova, J. V. Kopeina, G. Sivakov, V. Osminkina, L. A. Lorenz, K. |
author_facet | Tolstik, E. Gongalsky, M. B. Dierks, J. Brand, T. Pernecker, M. Pervushin, N. V. Maksutova, D. E. Gonchar, K. A. Samsonova, J. V. Kopeina, G. Sivakov, V. Osminkina, L. A. Lorenz, K. |
author_sort | Tolstik, E. |
collection | PubMed |
description | Nanomaterials are a central pillar in modern medicine. They are thought to optimize drug delivery, enhance therapeutic efficacy, and reduce side-effects. To foster this technology, analytical methods are needed to validate not only the localization and distribution of these nanomaterials, but also their compatibility with cells, drugs, and drug release. In the present work, we assessed nanoparticles based on porous silicon (pSiNPs) loaded with the clinically used tyrosine kinase inhibitor sunitinib for their effectiveness of drug delivery, release, and toxicity in colon cancer cells (HCT 116 cells) and cardiac myoblast cells (H9c2) using Raman micro-spectroscopy, high-resolution fluorescence microscopy, along with biological methods for toxicological effects. We produced pSiNPs with a size of about 100 nm by grinding mesoporous silicon layers. pSiNPs allowed an effective loading of sunitinib due to their high porosity. Photoluminescence properties of the nanoparticles within the visible spectrum allowed the visualization of their uptake in cardiac cells. Raman micro-spectroscopy allowed not only the detection of the uptake and distribution of pSiNPs within the cells via a characteristic silicon Raman band at about 518–520 cm(−1), but also the localization of the drug based on its characteristic molecular fingerprints. Cytotoxicity studies by Western blot analyses of apoptotic marker proteins such as caspase-3, and the detection of apoptosis by subG1-positive cell fractions in HCT 116 and MTT analyses in H9c2 cells, suggest a sustained release of sunitinib from pSiNPs and delayed cytotoxicity of sunitinib in HCT 116 cells. The analyses in cardiac cells revealed that pSiNPs are well tolerated and that they may even protect from toxic effects in these cells to some extent. Analyses of the integrity of mitochondrial networks as an early indicator for apoptotic cellular effects seem to validate these observations. Our study suggests pSiNPs-based nanocontainers for efficient and safe drug delivery and Raman micro-spectroscopy as a reliable method for their detection and monitoring. Thus, the herein presented nanocontainers and analytical methods have the potential to allow an efficient advancement of nanoparticles for targeted and sustained intracellular drug release that is of need, e.g., in chronic diseases and for the prevention of cardiac toxicity. |
format | Online Article Text |
id | pubmed-9397571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93975712022-08-24 Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells Tolstik, E. Gongalsky, M. B. Dierks, J. Brand, T. Pernecker, M. Pervushin, N. V. Maksutova, D. E. Gonchar, K. A. Samsonova, J. V. Kopeina, G. Sivakov, V. Osminkina, L. A. Lorenz, K. Front Pharmacol Pharmacology Nanomaterials are a central pillar in modern medicine. They are thought to optimize drug delivery, enhance therapeutic efficacy, and reduce side-effects. To foster this technology, analytical methods are needed to validate not only the localization and distribution of these nanomaterials, but also their compatibility with cells, drugs, and drug release. In the present work, we assessed nanoparticles based on porous silicon (pSiNPs) loaded with the clinically used tyrosine kinase inhibitor sunitinib for their effectiveness of drug delivery, release, and toxicity in colon cancer cells (HCT 116 cells) and cardiac myoblast cells (H9c2) using Raman micro-spectroscopy, high-resolution fluorescence microscopy, along with biological methods for toxicological effects. We produced pSiNPs with a size of about 100 nm by grinding mesoporous silicon layers. pSiNPs allowed an effective loading of sunitinib due to their high porosity. Photoluminescence properties of the nanoparticles within the visible spectrum allowed the visualization of their uptake in cardiac cells. Raman micro-spectroscopy allowed not only the detection of the uptake and distribution of pSiNPs within the cells via a characteristic silicon Raman band at about 518–520 cm(−1), but also the localization of the drug based on its characteristic molecular fingerprints. Cytotoxicity studies by Western blot analyses of apoptotic marker proteins such as caspase-3, and the detection of apoptosis by subG1-positive cell fractions in HCT 116 and MTT analyses in H9c2 cells, suggest a sustained release of sunitinib from pSiNPs and delayed cytotoxicity of sunitinib in HCT 116 cells. The analyses in cardiac cells revealed that pSiNPs are well tolerated and that they may even protect from toxic effects in these cells to some extent. Analyses of the integrity of mitochondrial networks as an early indicator for apoptotic cellular effects seem to validate these observations. Our study suggests pSiNPs-based nanocontainers for efficient and safe drug delivery and Raman micro-spectroscopy as a reliable method for their detection and monitoring. Thus, the herein presented nanocontainers and analytical methods have the potential to allow an efficient advancement of nanoparticles for targeted and sustained intracellular drug release that is of need, e.g., in chronic diseases and for the prevention of cardiac toxicity. Frontiers Media S.A. 2022-08-09 /pmc/articles/PMC9397571/ /pubmed/36016563 http://dx.doi.org/10.3389/fphar.2022.962763 Text en Copyright © 2022 Tolstik, Gongalsky, Dierks, Brand, Pernecker, Pervushin, Maksutova, Gonchar, Samsonova, Kopeina, Sivakov, Osminkina and Lorenz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Tolstik, E. Gongalsky, M. B. Dierks, J. Brand, T. Pernecker, M. Pervushin, N. V. Maksutova, D. E. Gonchar, K. A. Samsonova, J. V. Kopeina, G. Sivakov, V. Osminkina, L. A. Lorenz, K. Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells |
title | Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells |
title_full | Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells |
title_fullStr | Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells |
title_full_unstemmed | Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells |
title_short | Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells |
title_sort | raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397571/ https://www.ncbi.nlm.nih.gov/pubmed/36016563 http://dx.doi.org/10.3389/fphar.2022.962763 |
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