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Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer

Background: An advanced stage, centrally localized invasive tumor is a major cause of sudden death in lung cancer patients. Currently, chemotherapy, radiotherapy, laser ablation, or surgical resection if possible are the available state-of-the-art treatments but none of these guarantee remedy or lon...

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Autores principales: Ruzgys, Paulius, Böhringer, Stephan, Dokumaci, Ayse Sila, Hari, Yvonne, Schürch, Christian M., Brühl, Frido, Schürch, Stefan, Szidat, Sönke, Riether, Carsten, Šatkauskas, Saulius, Geiser, Thomas, Hradetzky, David, Gazdhar, Amiq
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093875/
https://www.ncbi.nlm.nih.gov/pubmed/33959011
http://dx.doi.org/10.3389/fphar.2021.643492
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author Ruzgys, Paulius
Böhringer, Stephan
Dokumaci, Ayse Sila
Hari, Yvonne
Schürch, Christian M.
Brühl, Frido
Schürch, Stefan
Szidat, Sönke
Riether, Carsten
Šatkauskas, Saulius
Geiser, Thomas
Hradetzky, David
Gazdhar, Amiq
author_facet Ruzgys, Paulius
Böhringer, Stephan
Dokumaci, Ayse Sila
Hari, Yvonne
Schürch, Christian M.
Brühl, Frido
Schürch, Stefan
Szidat, Sönke
Riether, Carsten
Šatkauskas, Saulius
Geiser, Thomas
Hradetzky, David
Gazdhar, Amiq
author_sort Ruzgys, Paulius
collection PubMed
description Background: An advanced stage, centrally localized invasive tumor is a major cause of sudden death in lung cancer patients. Currently, chemotherapy, radiotherapy, laser ablation, or surgical resection if possible are the available state-of-the-art treatments but none of these guarantee remedy or long-term relief and are often associated with fatal complications. Allowing localized chemotherapy, by direct and confined drug delivery only at the tumor site, could be a promising option for preoperative down staging or palliative therapy. Here we report the localized and targeted application of intra tumor delivery of chemotherapeutics using a novel device based on the principle of electrospray. Methods: C57BL/6J mice were injected with Lewis lung carcinoma cells subcutaneously. After 15 days, the animals were anesthetized and the tumors were exposed by skin incision. Tumors were electrosprayed with 100 µg cisplatin on days 0 and 2, and tumor volumes were measured daily. Animals were sacrificed on day 7 after the first electrospray and tumors were analyzed by immunohistochemistry. Results: In this proof-of-concept study, we report that the tumor volume was reduced by 81.2% (22.46 ± 12.14 mm(3)) after two electrospray mediated Cisplatin deliveries, while the control tumor growth, at the same time point, increased by 200% (514.30 ± 104.50 mm(3)). Moreover, tunnel and Caspase-3 positive cells were increased after Cisplatin electrospray compared to other experimental groups of animals. Conclusion: Targeted drug delivery by electrospray is efficient in the subcutaneous mouse model of lung cancer and offers a promising opportunity for further development toward its clinical application.
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spelling pubmed-80938752021-05-05 Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer Ruzgys, Paulius Böhringer, Stephan Dokumaci, Ayse Sila Hari, Yvonne Schürch, Christian M. Brühl, Frido Schürch, Stefan Szidat, Sönke Riether, Carsten Šatkauskas, Saulius Geiser, Thomas Hradetzky, David Gazdhar, Amiq Front Pharmacol Pharmacology Background: An advanced stage, centrally localized invasive tumor is a major cause of sudden death in lung cancer patients. Currently, chemotherapy, radiotherapy, laser ablation, or surgical resection if possible are the available state-of-the-art treatments but none of these guarantee remedy or long-term relief and are often associated with fatal complications. Allowing localized chemotherapy, by direct and confined drug delivery only at the tumor site, could be a promising option for preoperative down staging or palliative therapy. Here we report the localized and targeted application of intra tumor delivery of chemotherapeutics using a novel device based on the principle of electrospray. Methods: C57BL/6J mice were injected with Lewis lung carcinoma cells subcutaneously. After 15 days, the animals were anesthetized and the tumors were exposed by skin incision. Tumors were electrosprayed with 100 µg cisplatin on days 0 and 2, and tumor volumes were measured daily. Animals were sacrificed on day 7 after the first electrospray and tumors were analyzed by immunohistochemistry. Results: In this proof-of-concept study, we report that the tumor volume was reduced by 81.2% (22.46 ± 12.14 mm(3)) after two electrospray mediated Cisplatin deliveries, while the control tumor growth, at the same time point, increased by 200% (514.30 ± 104.50 mm(3)). Moreover, tunnel and Caspase-3 positive cells were increased after Cisplatin electrospray compared to other experimental groups of animals. Conclusion: Targeted drug delivery by electrospray is efficient in the subcutaneous mouse model of lung cancer and offers a promising opportunity for further development toward its clinical application. Frontiers Media S.A. 2021-04-20 /pmc/articles/PMC8093875/ /pubmed/33959011 http://dx.doi.org/10.3389/fphar.2021.643492 Text en Copyright © 2021 Ruzgys, Böhringer, Dokumaci, Hari, Schürch, Brühl, Schürch, Szidat, Riether, Šatkauskas, Geiser, Hradetzky and Gazdhar. 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
Ruzgys, Paulius
Böhringer, Stephan
Dokumaci, Ayse Sila
Hari, Yvonne
Schürch, Christian M.
Brühl, Frido
Schürch, Stefan
Szidat, Sönke
Riether, Carsten
Šatkauskas, Saulius
Geiser, Thomas
Hradetzky, David
Gazdhar, Amiq
Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer
title Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer
title_full Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer
title_fullStr Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer
title_full_unstemmed Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer
title_short Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer
title_sort electrospray mediated localized and targeted chemotherapy in a mouse model of lung cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093875/
https://www.ncbi.nlm.nih.gov/pubmed/33959011
http://dx.doi.org/10.3389/fphar.2021.643492
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