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Morphological Response in Cancer Spheroids for Screening Photodynamic Therapy Parameters

Authors :
Jose R. Aguilar Cosme
Dan C. Gagui
Helen E. Bryant
Frederik Claeyssens
Source :
Frontiers in Molecular Biosciences, Vol 8 (2021), Frontiers in Molecular Biosciences
Publication Year :
2021
Publisher :
Frontiers Media SA, 2021.

Abstract

Photodynamic therapy (PDT) is a treatment which uses light-activated compounds to produce reactive oxygen species, leading to membrane damage and cell death. Multicellular cancer spheroids are a preferable alternative for PDT evaluation in comparison to monolayer cell cultures due to their ability to better mimic in vivo avascular tumour characteristics such as hypoxia and cell-cell interactions, low cost, and ease of production. However, inconsistent growth kinetics and drug responsiveness causes poor experimental reproducibility and limits their usefulness. Herein, we used image analysis to establish a link between human melanoma C8161 spheroid morphology and drug responsiveness. Spheroids were pre-selected based on sphericity, area, and diameter, reducing variation in experimental groups before treatment. Spheroid morphology after PDT was analyzed using AnaSP and ReViSP, MATLAB-based open-source software, obtaining nine different parameters. Spheroids displayed a linear response between biological assays and morphology, with area (R2 = 0.7219) and volume (R2 = 0.6138) showing the best fit. Sphericity, convexity, and solidity were confirmed as poor standalone indicators of spheroid viability. Our results indicate spheroid morphometric parameters can be used to accurately screen inefficient treatment combinations of novel compounds.

Details

ISSN :
2296889X
Volume :
8
Database :
OpenAIRE
Journal :
Frontiers in Molecular Biosciences
Accession number :
edsair.doi.dedup.....478d7db3b60d94d9b9a5ea087bd25191
Full Text :
https://doi.org/10.3389/fmolb.2021.784962