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. Author manuscript; available in PMC: 2020 Mar 9.
Published in final edited form as: Nat Catal. 2019 Sep 9;2(10):864–872. doi: 10.1038/s41929-019-0333-4

Figure 4. Design and synthesis of prodrug 4 and targeted intracellular activation mediated by Pd-ExoA549 and Pd-ExoU87 in A549 and U87 cells.

Figure 4

(a) Intracellular Pd-ExoA549-mediated conversion of prodrug 4 into clinically-approved HDAC inhibitor 3. (b) Total synthesis of compound 4. (c) Pd-ExoA549-mediated uncaging of 4 inside cells. A549 and U87 cells were incubated for 6 h with 0.4 and 0.53 μg / 100 μL, respectively. Cells were thoroughly washed to eliminate extracellular vesicles followed by addition of prodrug 4 (0.2 μM). Controls: Pd-ExoA549 only (–ve control, grey); prodrug 4 only (–ve control, purple); 3 (+ve control, green). Cell viability was measured at day 5 using PrestoBlue. Error bars: ± SEM, n = 3. (d) Pd-ExoU87-mediated uncaging of 4 inside cells. A549 and U87 cells were incubated for 6 h with 0.4 and 0.53 μg / 100 μL, respectively. Cells were thoroughly washed to eliminate extracellular vesicles followed by addition of prodrug 4 (0.2 μM). Controls: Pd-ExoU87 only (–ve control, grey); prodrug 4 only (–ve control, purple); 3 (+ve control, green). Cell viability was measured at day 5 using PrestoBlue. Error bars: ± SEM, n = 3.