Tissue selective affinity targeting using the avidin-biotin system

Selective delivery of biologically active substances is designed to overcom e nonspecific biodistribution of drugs and increase their local concentrati on at the target tissue. Certain strategies are based on carrier-mediated d elivery to selective tissues and organs through ligands recognized by recep tors or other address molecules on target cells. Avidins offer an attractiv e approach to organ- or tissue-selective targeting. Avidin and streptavidin , two biotin-binding proteins, can be targeted to specific tissues when mod ified with appropriate tissue markers. Their resistance to proteolytic enzy mes supports long-term accumulation at the target tissue or organ, and thei r biotin binding sites permit the delivery of biotinylated molecules or car riers loaded with cytotoxic drugs or other bioactive substances. Modificati on of the two proteins with tissue-specific markers (lactose for parenchyma l and trinitrophenyl for nonparenchymal liver cells) resulted in high and p rolonged accumulation in the target tissue. The modified proteins could tar get high doses of chemotherapeutic drugs (CDDP and 5-fluorouridine) to the liver through biotinyl dextran-derived carriers. Drug Dev. Res. 50:258-271, 2000. (C) 2000 Wiley-Liss, Inc.