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. 2020 Sep 17;8:553576. doi: 10.3389/fcell.2020.553576

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Copyright © 2020 Pisano, Pierini, Gu, Gazze, Francis, Gonzalez, Conlan and Corradetti.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Cell proliferation assessed by Alamar blue and xCELLigence eSight analysis of cell index. (A) Percentage of viable cells following the treatment with doxorubicin-loaded IDEM (IDEM-DOXO) and EXO (EXO-DOXO) at 1 μg/mL. Alamar blue assay was used to quantify the percentage of viable cells over a 96-h period. IDEM- and EXO-DOXO are statistically more cytotoxic than the free doxorubicin formulation (10 μg/mL, DOXO) at 48, 72, and 96 h time points (p* < 0.05). A two-tail T-test was performed to assess for statistical significance compared to free doxorubicin formulation (DOXO, p* < 0.05). (B) Percentage of SKOV-3 viable cells following the treatment with IDEM-DOXO and EXO-DOXO at 3 μg/mL. EXO-DOXO were more effective than free doxorubicin (DOXO) in causing cell cytotoxicity on SKOV-3 cells at all time points (p** < 0.01 at 24 and 48 h, p* < 0.05 at 72 and 96 h respectively) while IDEM-DOXO were significantly more effective at 24 and 48 h time points (p* < 0.05), both formulations reaching more than 50% reduction in viability as soon as 24 h after the beginning of the experiment. (C) Cell index analysis of 1 μg/mL of IDEM-DOXO and EXO-DOXO over time, showing a marked decrease in cell index compared to untreated control after up to 110 h. (D) Cell index analysis of 3 μg/mL of IDEM-DOXO and EXO-DOXO have a similar effect to free DOXO in reducing cell proliferation of SKOV-3 cells for a time period of up to 110 h.