Esterase-Responsive Mitochondria-Targeted Hydropersulfide Donors Mitigate Doxorubicin Cardiotoxicity While Preserving Anticancer Activity.

In addition, we observed significant increases in Cys-SH and GSH in the cytoplasm upon treatment with APT-1 and APT-1-TPP , whereas in mitochondria, modest increases were observed with both donors that did not reach statistical significance ( Figure S22 ) Given the intracellular abundance of thiols, donor consumption through thiol–disulfide exchange or premature ester hydrolysis in the cytosol could potentially interfere with mitochondrial targeting.

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