Selective energy depletion and sensitization of multiple drug-resistant cancer cells by pluronic block copolymer

This work demonstrates that exposure of cells to a poly(ethylene oxide)-pol y(propylene oxide) block copolymer, Pluronic P85, results in substantial de crease in ATP levels selectively in MDR cells. Cells expressing high levels of P-glycoprotein are highly responsive to the Pluronic treatment, while t hose with low levels of expression are much less responsive. Cytotoxicity s tudies suggest that Pluronic acts as a chemosensitizer and potentiates cyto toxic effects of doxorubicin in MDR cells. Because many mechanisms of drug resistance are energy-dependent, a successful strategy for treating MDR can cer could be based on selective energy depletion in MDR cells. Therefore, t he finding of energy-depleting effects of Pluronic P85, in combination with its sensitization effects is of considerable theoretical and practical sig nificance.