Cytotoxicity of selected water-soluble polymer-cis-diaminedichloroplatinum(II) conjugates against the human HeLa cancer cell line

Several polymer-platinum conjugates comprising the square-planar cis-diamine-dichloroplatinum( II) complex system of cisplatin-type anticancer drugs are screened for antiproliferative activity in cell culture tests. The water-soluble conjugates prepared in this study or taken From preceding investigations are obtained by platination of aliphatic polyamide carriers containing ethylenediamine segments as side-group or main-chain components. These segments, coordinating to the metal as cis-diamine chelating ligands, are bound to, or into, the carrier backbone through biofissionable amide links permitting drug release From the carrier. In uiti.o tests are performed against a HeLa human cervix carcinoma cell line. IC50 data, expressed as the concentration of Pt in the conjugates (mu g/ml), causing 50% inhibition of cell growth, show the highest activity, with IC50 = 14 mu g/ml, to be associated with a conjugate derived from a polyaspartamide carrier that contains the platinum complex as a side group in proximity to the main chain and, additionally, contains dimethylaminopropyl side groups as solubilizing functions. At the low end of the performance spectrum is a conjugate, with IC50 > 120 mu g/ml, possessing a similar backbone and metal-binding structure, yet comprising long poly(ethylene oxide) grafts. The latter apparently shield the complex-binding tether From enzymatic attack and thus prevent efficient intracellular release of the monomeric complex. Selected conjugates will be submitted for toxicological evaluation.