RECEPTOR-MEDIATED TRANSPORT OF BIOLOGICALLY-ACTIVE SUBSTANCES INTO CELLS USING RECOMBINANT HUMAN GROWTH-HORMONE

The possibility of intracellular delivery of biologically active subst ances (BAS) by receptor-mediated endocytosis was studied. The problem of transfer is essential for those BAS, including oligonucleotides, wh ich are not able to pass through the cell membranes in free state. Hum an growth hormone (HGH) was chosen as a vector, because its receptors are present in all human cells and are known to be actively endocytize d. Doxorubicin (DR) was used as a model BAS. Its accumulation was foll owed by fluorescence measurements and its biological activity by cytot oxicity tests. Free DR and DR conjugated with HGH (3:1-30:1molar ratio ) were used. When the conjugated preparations were incubated with the cells expressing lactogenic (line Nb2-11C) or somatotropic (line Im-9) receptors, DR was accumulated in these cells, with about 80% intercal ation into nuclear DNA. The cytotoxicity of conjugated DR/HGH preparat ions and free DR was similar, HGH may be used for efficient translocat ion of various BAS into mammalian cells.