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Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method

Photochemical internalisation (PCI) is a means of achieving spatio-temporal control of cytosolic drug delivery using sub-lethal photodynamic therapy (PDT), with a photosensitiser that can be activated by non-ionising visible light. Various 3D models including those developed at our laboratory, where...

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Autores principales: Mohammad Hadi, Layla, Stamati, Katerina, Yaghini, Elnaz, MacRobert, Alexander J., Loizidou, Marilena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953023/
https://www.ncbi.nlm.nih.gov/pubmed/36831108
http://dx.doi.org/10.3390/biomedicines11020572
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author Mohammad Hadi, Layla
Stamati, Katerina
Yaghini, Elnaz
MacRobert, Alexander J.
Loizidou, Marilena
author_facet Mohammad Hadi, Layla
Stamati, Katerina
Yaghini, Elnaz
MacRobert, Alexander J.
Loizidou, Marilena
author_sort Mohammad Hadi, Layla
collection PubMed
description Photochemical internalisation (PCI) is a means of achieving spatio-temporal control of cytosolic drug delivery using sub-lethal photodynamic therapy (PDT), with a photosensitiser that can be activated by non-ionising visible light. Various 3D models including those developed at our laboratory, where spheroids are grown in a compressed collagen matrix, have been used for studying anti-cancer drug effects. However, the use of a more biomimetic tumouroid model which consists of a relatively hypoxic central cancer mass surrounded by its microenvironment (stroma) has not yet been explored in either toxicity or phototoxicity studies involving PCI. Here, we examined the efficacy of PCI using a porphyrin photosensitiser and a cytotoxin (Saporin) on ovarian cancer tumouroids, with HEY ovarian cancer cells in the central cancer compartment, and HDF fibroblast cells and HUVEC endothelial cells in the surrounding stromal compartment. The efficacy was compared to tumouroids treated with either Saporin or PDT alone, or no treatment. PCI treatment was shown to be effective in the tumouroids (determined through viability assays and imaging) and caused a considerable decrease in the viability of cancer cells both within the central cancer mass and those which had migrated into the stroma, as well as a reduction in the cell density of surrounding HUVEC and HDFs. Post-treatment, the mean distance of stromal invasion by cancer cells from the original cancer mass following treatment with Saporin alone was 730 μm vs. 125 μm for PCI. PDT was also effective at reducing viability in the central cancer mass and stroma but required a higher photosensitiser dose and light dose than PCI. Tumouroids, as tissue mimics, are suitable models for interrogating multicellular events following pharmacological assault.
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spelling pubmed-99530232023-02-25 Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method Mohammad Hadi, Layla Stamati, Katerina Yaghini, Elnaz MacRobert, Alexander J. Loizidou, Marilena Biomedicines Article Photochemical internalisation (PCI) is a means of achieving spatio-temporal control of cytosolic drug delivery using sub-lethal photodynamic therapy (PDT), with a photosensitiser that can be activated by non-ionising visible light. Various 3D models including those developed at our laboratory, where spheroids are grown in a compressed collagen matrix, have been used for studying anti-cancer drug effects. However, the use of a more biomimetic tumouroid model which consists of a relatively hypoxic central cancer mass surrounded by its microenvironment (stroma) has not yet been explored in either toxicity or phototoxicity studies involving PCI. Here, we examined the efficacy of PCI using a porphyrin photosensitiser and a cytotoxin (Saporin) on ovarian cancer tumouroids, with HEY ovarian cancer cells in the central cancer compartment, and HDF fibroblast cells and HUVEC endothelial cells in the surrounding stromal compartment. The efficacy was compared to tumouroids treated with either Saporin or PDT alone, or no treatment. PCI treatment was shown to be effective in the tumouroids (determined through viability assays and imaging) and caused a considerable decrease in the viability of cancer cells both within the central cancer mass and those which had migrated into the stroma, as well as a reduction in the cell density of surrounding HUVEC and HDFs. Post-treatment, the mean distance of stromal invasion by cancer cells from the original cancer mass following treatment with Saporin alone was 730 μm vs. 125 μm for PCI. PDT was also effective at reducing viability in the central cancer mass and stroma but required a higher photosensitiser dose and light dose than PCI. Tumouroids, as tissue mimics, are suitable models for interrogating multicellular events following pharmacological assault. MDPI 2023-02-15 /pmc/articles/PMC9953023/ /pubmed/36831108 http://dx.doi.org/10.3390/biomedicines11020572 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
Mohammad Hadi, Layla
Stamati, Katerina
Yaghini, Elnaz
MacRobert, Alexander J.
Loizidou, Marilena
Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method
title Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method
title_full Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method
title_fullStr Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method
title_full_unstemmed Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method
title_short Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method
title_sort treatment of 3d in vitro tumoroids of ovarian cancer using photochemical internalisation as a drug delivery method
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953023/
https://www.ncbi.nlm.nih.gov/pubmed/36831108
http://dx.doi.org/10.3390/biomedicines11020572
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