RECEPTOR-TARGETED DELIVERY OF AN INTRACELLULAR TOXIN TO OUTER HAIR-CELLS BY FIBROBLAST GROWTH-FACTOR

The presence and distribution of functional, high-affinity receptors f or fibroblast growth factors (FGFs) in the neonatal organ of Corti wer e probed using the intracellular toxin saporin conjugated to basic FGF (FGF-2). FGFs that bind to high-affinity FGF receptors are internaliz ed as part of the normal process of receptor inactivation. The recepto r can thus be used for the targeted delivery of molecules conjugated t o FGF into the cytoplasm. Incubation of postnatal day 5 (P5) rat organ of Corti cultures with FGF-saporin caused a dose dependent destructio n of outer hair cells, Deiters cells and outer pillar cells. Inner hai r cells and other cells were unaffected. Organ of Corti cultures at P0 and P10 showed much less damage than at P5. The results suggest that outer hair cells and adjacent supporting cells in the organ of Corti t ransiently express high-affinity FGF receptors, and that these recepto rs can mediate the intracellular delivery of bioactive molecules. (C) 1998 Elsevier Science B.V.