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The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry

Microbubble (MB)- and ultrasound (US)-facilitated intracellular Ca(2+) delivery, known as sonoporation (SP), is a promising anticancer treatment modality, since it allows a spatio-temporally controllable and side-effect-free alternative to conventional chemotherapy. The current study provides extens...

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Autores principales: Maciulevičius, Martynas, Raišutis, Renaldas, Jakštys, Baltramiejus, Svilainis, Linas, Chaziachmetovas, Andrius, Šatkauskas, Saulius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221366/
https://www.ncbi.nlm.nih.gov/pubmed/37242705
http://dx.doi.org/10.3390/pharmaceutics15051463
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author Maciulevičius, Martynas
Raišutis, Renaldas
Jakštys, Baltramiejus
Svilainis, Linas
Chaziachmetovas, Andrius
Šatkauskas, Saulius
author_facet Maciulevičius, Martynas
Raišutis, Renaldas
Jakštys, Baltramiejus
Svilainis, Linas
Chaziachmetovas, Andrius
Šatkauskas, Saulius
author_sort Maciulevičius, Martynas
collection PubMed
description Microbubble (MB)- and ultrasound (US)-facilitated intracellular Ca(2+) delivery, known as sonoporation (SP), is a promising anticancer treatment modality, since it allows a spatio-temporally controllable and side-effect-free alternative to conventional chemotherapy. The current study provides extensive evidence that a 5 mM concentration of Ca(2+) in combination with US alone or US and Sonovue MBs can be an alternative to the conventional 20 nM concentration of the anticancer drug bleomycin (BLM). Ca(2+) application together with SP induces a similar level of death in Chinese hamster ovary cells to the combination of BLM and SP but does not cause systemic toxicity, as is inherent to conventional anticancer drugs. In addition, Ca(2+) delivery via SP alters three vital characteristics essential for viable cells: membrane permeability, metabolic activity and proliferation ability. Most importantly, Ca(2+) delivery via SP elicits sudden cell death—occurring within 15 min—which remains similar during 24–72 h and 6 d periods. The extensive study of US waves side-scattered by MBs led to the quantification of the cavitation dose (CD) separately for subharmonics, ultraharmonics, harmonics and broadband noise (up to 4 MHz). The CD was suitable for the prognostication of the cytotoxic efficiency of both anticancer agents, Ca(2+) and BLM, as was indicated by an overall high (R(2) ≥ 0.8) correlation (22 pairs in total). These extensive analytical data imply that a broad range of frequencies are applicable for the feedback-loop control of the process of US-mediated Ca(2+) or BLM delivery, successively leading to the eventual standardization of the protocols for the sonotransfer of anticancer agents as well as the establishment of a universal cavitation dosimetry model.
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spelling pubmed-102213662023-05-28 The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry Maciulevičius, Martynas Raišutis, Renaldas Jakštys, Baltramiejus Svilainis, Linas Chaziachmetovas, Andrius Šatkauskas, Saulius Pharmaceutics Article Microbubble (MB)- and ultrasound (US)-facilitated intracellular Ca(2+) delivery, known as sonoporation (SP), is a promising anticancer treatment modality, since it allows a spatio-temporally controllable and side-effect-free alternative to conventional chemotherapy. The current study provides extensive evidence that a 5 mM concentration of Ca(2+) in combination with US alone or US and Sonovue MBs can be an alternative to the conventional 20 nM concentration of the anticancer drug bleomycin (BLM). Ca(2+) application together with SP induces a similar level of death in Chinese hamster ovary cells to the combination of BLM and SP but does not cause systemic toxicity, as is inherent to conventional anticancer drugs. In addition, Ca(2+) delivery via SP alters three vital characteristics essential for viable cells: membrane permeability, metabolic activity and proliferation ability. Most importantly, Ca(2+) delivery via SP elicits sudden cell death—occurring within 15 min—which remains similar during 24–72 h and 6 d periods. The extensive study of US waves side-scattered by MBs led to the quantification of the cavitation dose (CD) separately for subharmonics, ultraharmonics, harmonics and broadband noise (up to 4 MHz). The CD was suitable for the prognostication of the cytotoxic efficiency of both anticancer agents, Ca(2+) and BLM, as was indicated by an overall high (R(2) ≥ 0.8) correlation (22 pairs in total). These extensive analytical data imply that a broad range of frequencies are applicable for the feedback-loop control of the process of US-mediated Ca(2+) or BLM delivery, successively leading to the eventual standardization of the protocols for the sonotransfer of anticancer agents as well as the establishment of a universal cavitation dosimetry model. MDPI 2023-05-11 /pmc/articles/PMC10221366/ /pubmed/37242705 http://dx.doi.org/10.3390/pharmaceutics15051463 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Maciulevičius, Martynas
Raišutis, Renaldas
Jakštys, Baltramiejus
Svilainis, Linas
Chaziachmetovas, Andrius
Šatkauskas, Saulius
The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry
title The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry
title_full The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry
title_fullStr The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry
title_full_unstemmed The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry
title_short The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry
title_sort assessment of calcium and bleomycin cytotoxic efficiency in relation to cavitation dosimetry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10221366/
https://www.ncbi.nlm.nih.gov/pubmed/37242705
http://dx.doi.org/10.3390/pharmaceutics15051463
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