Slow release of etoposide from dextran conjugation shifts etoposide activity from cytotoxicity to differentiation: A promising tool for dosage control in anticancer metronomic therapy

Linking the antitumor drug etoposide via pH-sensitive bond to dextran produced slow drug-releasing conjugates and changed the dynamics of drug availability with respect to the nominal concentration. This assured tumor cell elimination but shifted the modality of apoptosis from cytotoxicity (= that induced by one-shot high dose) to physiological differentiation (= that induced by repeated, lower doses of anticancer drug). Therefore, conjugation may be a useful tool to control drug dosage in the emerging anticancer metronomic strategy, which is based on the continuous presence of low drug doses.68