Cis-diamminedichloroplatinum(II), or Cisplatin, is a commercially- available anti-tumor agent used to effectively treat testicular, ovarian, cervical, bladder, and head/neck tumors. Unfortunately, there are several problems with Cisplatin which limit its clinical use including insolubility in saline, severe toxic side effects in patients, such as renal toxicity and nausea, and acquired resistance by cancer cells. One way to combat these drawbacks might be to attach the Cisplatin or derivative to gadolinium(III) texaphyrin (Gd-tex2+) which would act as a water-soluble carrier to deliver the Pt complex site specifically. Gd-tex2+ selectively increases cytotoxicity in cell lines when it is applied as a radiosensitizer in X-ray therapy. The lutetium analog, Lu-tex2+, has been found to act as a photosensitizer to enhance the effectiveness of photodynamic therapy. Both of these lanthanide complexes, which, unlike Cisplatin, are cleared hepatically, are in the clinic as Investigational New Drugs and have shown positive results. The design and synthesis of Cisplatin-texaphyrin conjugates could be accomplished by linking the Pt derivative to the texaphyrin through ligands which would hold the two agents intact throughout drug delivery and action or through ligands which would dissociate the platinum complex once inside the cancer cell. Numerous synthetic strategies will be used to modify the texaphyrin macrocycle to attach a Cisplatin derivative. The bifunctional products will be characterized and checked for parameters that correlate with effective X-ray and photodynamic therapy activity (e.g.,electrochemistry, fluorescence) and for DNA interaction.
