Abstract
Several polymer-platinum conjugates comprising the square-planar cis-diaminedichloroplatinum(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 vitro tests are performed against a HeLa human cervix carcinoma cell line. IC50 data, expressed as the concentration of Pt in the conjugates (μg/ml), causing 50% inhibition of cell growth, show the highest activity, with IC50=14 μg/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 μg/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.
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Caldwell, G., Neuse, E.W. & van Rensburg, C.E.J. Cytotoxicity of Selected Water-Soluble Polymer–cis-Diaminedichloroplatinum(II) Conjugates Against the Human HeLa Cancer Cell Line. Journal of Inorganic and Organometallic Polymers 7, 217–231 (1997). https://doi.org/10.1023/A:1021642507614
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DOI: https://doi.org/10.1023/A:1021642507614