Macromolecular metal compounds in cancer research: Concepts and synthetic approaches

The anticancer activity of metal compounds has been a topic of major interest in drug research for two decades. Platinum compounds, in particular, including cisplatin (cis‐diamminedichloroplatinum(II)) and second generation derivatives, have for many years been among the leading drugs administered in clinical cancer therapy, although excessive toxicity, induction of drug resistance, and other formidable, detrimental side effects continue to militate against efficacious utilization and achievement of satisfactory cure rates. Adding to the toxicity problem, most bioactive metal complexes dissolve poorly, if at all, in aqueous media, possess low stability in solution, undergo rapid depletion from central circulation, and often times are prevented from smooth cell entry by molecular charge or polarity. The concept of polymer‐drug conjugation, designed to overcome the pharmacokinetic barriers to satisfactory clinical chemotherapy with present‐day anticancer drugs, is finding increasing acceptance in biomedical research. The concept has been utilized in our laboratory for the purpose of enhancing the effectiveness of metal‐containing carcinostatic agents. In the present communication we demonstrate the practicability of synthesizing platinum‐, iron‐, and tin‐containing polymer conjugates that are biodegradable, dissolve completely in water, and are structurally designed so as to permit release of the active metal compound in the biological environment. Following a brief review of initial results, we discuss selected synthetic approaches and obtained conjugates, in which the metals are bound to polymer‐attached ligands as dichloroplatinum(II), di‐η 5 ‐cyclopentadienyliron, and diorganotin(IV) moieties.