Methods for administering mitomycin C to a multi-drug resistant cell and
for reducing the toxicity of the compound are described. In the methods,
mitoymic C is provided in the form of a prodrug conjugate, where the drug
is linked to a hydrophobic moiety, such as a lipid, through a cleavable
dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage
by mild thiolysis, resulting in release of mitomycin C in its original
form. The linkage is stable under nonreducing conditions. The prodrug
conjugate can be incorporated into liposomes for administration in vivo
and release of mitomycin C in response to endogenous in vivo reducing
conditions or in response to administration of an exogenous reducing
agent.