Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/108315
Title: Cancer cell spheroids are a better screen for the photodynamic efficiency of glycosylated photosensitizers
Authors: Pereira, Patrícia M. R. 
Berisha, Naxhije
Bhupathiraju, N. V. S. Dinesh K.
Fernandes, Rosa 
Tomé, João P. C. 
Drain, Charles Michael
Issue Date: 2017
Publisher: Public Library of Science
Project: FCT/MEC financial support to QOPNA (FCTUID/QUI/00062/ 2013), IBILI (FCTUID/NEU/04539/2013) and CQE (FCTUID/QUI/0100/2013) research units, through national funds and where applicable cofinanced by the FEDER, within the PT2020 Partnership Agreement. 
ACIMAGO (ref. 12/12) 
Serial title, monograph or event: PLoS ONE
Volume: 12
Issue: 5
Abstract: Photodynamic Therapy (PDT) relies on the use of non-toxic photosensitizers that are locally and selectively activated by light to induce cell death or apoptosis through reactive oxygen species generation. The conjugation of porphyrinoids with sugars that target cancer is increasingly viewed as an effective way to increase the selectivity of PDT. To date, in vitro PDT efficacy is mostly screened using two-dimensional monolayer cultures. Compared to monolayer cultures, three-dimensional spheroid cultures have unique spatial distributions of nutrients, metabolites, oxygen and signalling molecules; therefore better mimic in vivo conditions. We obtained 0.05 mm3 spheroids with four different human tumor cell lines (HCT-116, MCF-7, UM-UC-3 and HeLa) with appropriate sizes for screening PDT agents. We observed that detachment from monolayer culture and growth as tumor spheroids was accompanied by changes in glucose metabolism, endogenous ROS levels, galectin-1 and glucose transporter GLUT1 protein levels. We compared the phototoxic responses of a porphyrin conjugated with four glucose molecules (PorGlu4) in monolayer and spheroid cultures. The uptake and phototoxicity of PorGlu4 is highly dependent on the monolayer versus spheroid model used and on the different levels of GLUT1 protein expressed by these in vitro platforms. This study demonstrates that HCT-116, MCF-7, UM-UC-3 and HeLa spheroids afford a more rational platform for the screening of new glycosylated-photosensitizers compared to monolayer cultures of these cancer cells.
URI: https://hdl.handle.net/10316/108315
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0177737
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
I&D IBILI - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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