Complexes and Conjugates of cis-Pt for Immunotargeted Chemotherapy
A major problem in cancer chemotherapy is how to enhance the effectiveness of currently available anti cancer drugs. Due to the lack of selectivity of cytotoxic agents, the administration of single drug doses is restricted to sub-toxic levels. Drug clearance and excretion and/or metabolic conversion of the drug result in only transient increased levels at the tumor site which are generally insufficient to effect complete cure. The problem is therefore, how to attain sufficient amounts of drug at the tumor site for the required period of time, without using drug doses which are above the threshold of toxicity. One possible way is to use molecules with inherent or acquired ability to interact selectively with the target organ, e.g. anti-tumor antibodies, as carriers for the drug, thus leading to specific targeting to the tumor site. An alternative approach is to attach anti-cancer agents to polymeric carriers that will act as control release units by affecting the biodistribution and maintenance of the drug. These delivery devices may cause retardation of drug clearance or inactivation as well as prolonged or sustained release of the drug at non-toxic levels, thus overcoming the problem of harmful peak concentrations. Such polymeric drug systems, in addition to being advantageous to the free drug as such, may be also used for conjugation to antitumor antibodies for the purpose of immunotargeting.
KeywordsToxicity Lymphoma Platinum Carboxyl Oncol
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- 3.R.F. Ozols and R.C. Young. High-dose cisplatin therapy in ovarian cancer. Semin. Oncol. 21:12 (1985).Google Scholar
- 4.J.J. Roberts. Mechanism of action of antitumor platinum compounds. In: Molecular mechanisms of carcinogenic and antitumor activity. C. Chagas and B. Pullman, eds. Pontificia Academia Scientiarvm. (1986).Google Scholar
- 5.M.E. Howe-Grant and S.J. Lippard. Aqueous platinum(II) chemistry: Binding to boilogical molecules. In: “Metal ions in biological systems”. H. Sigel, ed. Marcel Dekker, New York. 11:63 (1980).Google Scholar
- 6.D.A. Juckett and B. Rosenberg. Actions of cis-diamminedichloroplatinum on cell surface nucleic acids in cancer cells as determined by cell electrophoresis techniques. Cancer Res, 42:3562 (1982).Google Scholar
- 12.C.L. Litterst, T.E. Gram, R.L. Dedrick, A.F. Leroy and A.M. Guarino. Distribution and disposition of cis-diamminedichloroplatinum(II). (NCS-1198-75) in dogs. Cancer Res, 36: 2340 (1976).Google Scholar
- 13.B. Schechter, M.A. Rosing, M. Wilchek, and R. Arnon. Blood levels and serum-protein binding of cis-platinum(II) complexed to carboxymethyl-dextran. Cancer Chememother. Pharmacol, 24: 661 (1989).Google Scholar
- 17.D.J. Hnatowich, F. Virzi and M. Rusckowski. Investigations of avidin and biotin for imaging applications. J. Nuclear Med, 28: 1294 (1987).Google Scholar