ABSTRACT
Doxorubicin (DOX) is an anthracycline antibiotic widely used in the treatment of a variety of human cancers.1 It is a very potent drug showing a strong association between dose and antitumor response. As with other cytotoxic drugs, DOX is nonselectively cytotoxic and its clinical use is limited by myelosuppression and stomatitis. Furthermore, the repeated use of DOX is drastically limited by a cumulative, nonreversible cardiac damage, which appears to be related to mitochondrial damage caused by the semiquinone radical of anthracyclines.2 Clearly, any form of delivery that will shift the drug biodistribution into the tumor and away from the heart may result in a significant improvement of the therapeutic index of DOX. This goal has been pursued in a variety of ways from simple changes in the form of administration (continuous infusion as opposed to bolus injection3) through nonspecific delivery systems (drug-polymer conjugates) to sophisticated targeting devices (antibodies recognizing a membrane-associated antigen as vectors of the drug5).
