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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/2/572 |
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| author | Layla Mohammad Hadi Katerina Stamati Elnaz Yaghini Alexander J. MacRobert Marilena Loizidou |
| author_facet | Layla Mohammad Hadi Katerina Stamati Elnaz Yaghini Alexander J. MacRobert Marilena Loizidou |
| author_sort | Layla Mohammad Hadi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T09:06:57Z |
| format | Article |
| id | doaj.art-6b61d522c80e4678a5a0779f6ebf7200 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:06:57Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-6b61d522c80e4678a5a0779f6ebf72002023-11-16T19:20:13ZengMDPI AGBiomedicines2227-90592023-02-0111257210.3390/biomedicines11020572Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery MethodLayla Mohammad Hadi0Katerina Stamati1Elnaz Yaghini2Alexander J. MacRobert3Marilena Loizidou4Division of Surgery & Interventional Science, University College London, London NW3 2QG, UKDivision of Surgery & Interventional Science, University College London, London NW3 2QG, UKDivision of Surgery & Interventional Science, University College London, London NW3 2QG, UKDivision of Surgery & Interventional Science, University College London, London NW3 2QG, UKDivision of Surgery & Interventional Science, University College London, London NW3 2QG, UKPhotochemical 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.https://www.mdpi.com/2227-9059/11/2/572ovarian cancerphotochemical internalisationphotodynamic therapytumouroids3D compressed collagen constructhypoxia |
| spellingShingle | Layla Mohammad Hadi Katerina Stamati Elnaz Yaghini Alexander J. MacRobert Marilena Loizidou Treatment of 3D In Vitro Tumoroids of Ovarian Cancer Using Photochemical Internalisation as a Drug Delivery Method Biomedicines ovarian cancer photochemical internalisation photodynamic therapy tumouroids 3D compressed collagen construct hypoxia |
| 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 | ovarian cancer photochemical internalisation photodynamic therapy tumouroids 3D compressed collagen construct hypoxia |
| url | https://www.mdpi.com/2227-9059/11/2/572 |
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