Hepatic metastases of malignant tumors is a major problem in the treatment of cancers for which the liver is the most common site for recurrences. In the present study we describe a selective delivery system to the liver which may facilitate specific hepatic targeting of anti-cancer agents. Avidin and streptavidin are two biotin-binding proteins with extreme resistance to proteolytic activity. Trinitrophenyl (TNP) modification of these two proteins resulted in specific accumulation in mouse liver with levels of 40-50 percent per gram tissue (%/g) during a period of several days. The two modified proteins could target to the liver high doses of covalently bound radionuclide iodine-125, a biotinylated ligand such as biotinyl-tyrosine (BT) or large biotinylated carriers such as carboxymethyl dextran (CMdex, 40kDa). Appropriately derivatized dextrans serve as carriers for various chemotherapeutic drugs, as demonstrated here for cis-dichlorodiammineplatinum (CDDP). Specific liver targeting of CDDP complexed to CMdex-TNP-streptavidin could be monitored by flame atomic absorption spectrometry of the Pt metal: High levels of the Pt drug were concentrated in the liver for at least 15hr following its targeted delivery as compared to essentially undetectable levels after administration of the free drug.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.