Target-cell specificity of fusogenic liposomes: Membrane fusion-mediated macromolecule delivery into human blood mononuclear cells

Fusogenic liposome, a unique vector prepared by fusing ultraviolet-inactiva ted Sendai virus and liposome, is known to efficiently deliver content into various animal cells through membrane fusion. In this study, we examined t he target-cell specificity of fusogenic liposome (FL)-mediated macromolecul e delivery into human blood cells using diphtheria toxin fragment A (DTA) a s a probe. Among the peripheral blood mononuclear cells (PBMC), FL was able to deliver its encapsulates into CD14(+) monocytes and CD4(-)/CD8(-) T-cel ls, but not into CD19(+) B-lymphocytes, CD4(+) T-cells or CD8(+) T-cells. T he susceptibility of human leukemia cell lines to FL was similar to that of PBMC; the order of the reactivity was U937 (monoblastic leukemia)> MOLT4, Jurkat (T-lymphoma)> Daudi, BALL1 (B-lymphoma) > K562 (erythroblastic leuke mia). Interestingly, FL showed similar binding activity to all of these leu kemia cell lines. These findings indicate that, among blood cells, monocyte s, monoblastic leukemia cells, CD4(-)/CD8(-) T-cells and T-lymphoma cells a re preferable targets for FL-mediated macromolecule delivery. This is the f irst demonstration of the existence of non-permissive cells against FL. Our results also suggest that some molecules on target-cells other than the bi nding targets of SV-derived protein may participate in fusion between FL an d cells. (C) 1999 Elsevier Science B.V. All rights reserved.