The development of new in
vitro models
that closely
mimic the tumor microenvironment (TME) to evaluate the efficacy of
anticancer drugs has received great attention. In this study, a three-dimensional
(3D) bioprinted Michigan Cancer Foundation-7 (MCF-7) cancer spheroid-embedded
hydrogel model was suggested for integrative in situ determination of the half-maximal inhibitory concentration (IC50) values of photosensitizers (PSs). The MCF-7 cell-laden
alginate/gelatin hydrogel was printed for the fabrication of tumor
spheroids. The hydrogel was used to mimic the extracellular matrix
(ECM) surrounding the cancer cells in the TME. The fluorescence intensities
corresponding to photodynamic therapy (PDT)-induced death of tumor
spheroids probed by the laser showed a random distribution in the
hydrogel, regardless of the focus of the laser and the vertical-axis
direction in which the laser was passed. These results enabled integrative in situ measurement of all tumor spheroids probed by the
laser without needing to separate the tumor spheroids in the hydrogel
and measure them individually. When compared with two-dimensional
(2D) monolayer cultures, very large IC50 values of the
PSs, chlorin e6 (Ce6) and sulfonated tetraphenyl porphyrin (sTPP),
were achieved in MCF-7 spheroid-embedded hydrogels mainly due to the
drug resistance of the tumor spheroids. Additionally, the heterogenic
PDT response of single MCF-7 cancer cells in a single tumor spheroid
was observed through 3D imaging of irregular apoptosis in a single
spheroid since single tumor spheroids showed a heterogenic PDT response.
Furthermore, the laser-power-dependent IC50 values of PSs
were obtained using the MCF-7 spheroid-embedded hydrogel model.