Anticancer metal complexes and tumour targeting strategies

Cisplatin and carboplatin are at present two of the most widely used anticancer agents in the world. They show their best activity against testicular carcinomas and are also effective against ovarian carcinomas, tumours of the head and neck, and bladder tumours. The clinical responses seen with antitumour platinum complexes have incited the development of a number of non-platinum compounds with metal ions such as germanium(IV), titanium(IV), tin(IV), gallium(III) or ruthenium(III) which exhibit antitumour activity in in-vitro and in-vivo models. Some of these complexes have entered, or are about to enter, clinical trials. Although platinum and non-platinum complexes are potent antineoplastic agents, they do have serious side-effects (e.g. myelotoxicity, nephrotoxicity and neuropathy) that are due to their;reactions with cellular components of healthy tissues. Hence, to improve the selectivity of metal complexes for tumour tissue, effective drug delivery systems are needed. Appropriate carriers are low molecular weight compounds such as hormone derivatives, on the one hand, and macromolecular carriers or microparticles, on the other. Members of this latter group that are under investigation include microparticulate delivery systems (liposomes, nano- and microparticles, emulsions) and soluble polymeric delivery systems (serum proteins, synthetic and natural polymers). This review article describes antitumour metal complexes of preclinical and clinical interest and outlines tumour targeting concepts that use macromolecular and particulate carrier systems which aim to improve cancer chemotherapy with metal complexes.