Aguilar Cosme, J.R., Gagui, D.C., Green, N.H. orcid.org/0000-0001-5413-0642 et al. (2 more authors) (2021) In vitro low-fluence photodynamic therapy parameter screening using 3D tumor spheroids shows that fractionated light treatments enhance phototoxicity. ACS Biomaterials Science & Engineering, 7 (11). pp. 5078-5089. ISSN 2373-9878
Abstract
The evaluation of novel photosensitizers (PSs) for photodynamic therapy (PDT) is difficult due to the limitations of two-dimensional cell culture and multiple parameters (dose, light intensity, uptake time), which complicate progression to in vivo experiments and clinical translation. Three-dimensional (3D) cell culture models like multicellular cancer tumor spheroids (MCTS) show great similarities to in vivo avascular tumor conditions, improving the speed and accuracy of screening novel compounds with various treatment combinations. In this study, we utilize C8161 human melanoma spheroids to screen PDT treatment combinations using protoporphyrin IX (PpIX) and drug-loaded carbon dot (CD) conjugates PpIX-CD and PpIX@CD at ultralow fluence values (<10 J/cm2). Conjugates show equivalent light-induced damage to PpIX from 1 μg/mL with significantly less dark cytotoxicity up to 72 h after exposure, shown by LDH release and dsDNA content. Fractionated treatments, carried out by dividing light exposure with 24 h intervals, demonstrate an enhanced PDT effect compared to single exposure at equal concentrations. Light sheet fluorescence microscopy combined with live/dead staining demonstrates that spheroids sustain extensive damage after PDT, with PpIX and PpIX-CD showing improved uptake compared to PpIX@CD. We show that PDT parameter screening can be carried out using a low-cost and convenient combination of assays to improve the efficiency of evaluating novel compounds.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 American Chemical Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | photodynamic therapy; light fractionation; cancer spheroids; 3D cell culture; protoporphyrin IX; nanoparticles; carbon dots; light |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Materials Science and Engineering (Sheffield) |
Funding Information: | Funder Grant number Engineering and Physical Sciences Research Council EP/P02470X/1 Engineering and Physical Sciences Research Council EP/P025285/1 Engineering and Physical Sciences Research Council EP/S019367/1 Engineering and Physical Sciences Research Council EP/R00661X/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Nov 2021 10:45 |
Last Modified: | 15 Mar 2022 11:56 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/acsbiomaterials.1c00690 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:179807 |