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-inactivated Sendai virus and liposome, is known to efficiently deliver content into various animal cells through membrane fusion. In this study, we examined the target-cell specificity of fusogenic liposome (FL)-mediated macromolecule delivery into human blood cells using diphtheria toxin fragment A (DTA) as a probe. Among the peripheral blood mononuclear cells (PBMC), FL was able to deliver its encapsulates into CD14+ monocytes and CD4-/CD8- T-cells, but not into CD19+ B-lymphocytes, CD4+ T-cells or CD8+ T-cells. The 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 leukemia). Interestingly, FL showed similar binding activity to all of these leukemia cell lines. These findings indicate that, among blood cells, monocytes, monoblastic leukemia cells, CD4-/CD8- T-cells and T-lymphoma cells are preferable targets for FL-mediated macromolecule delivery. This is the first demonstration of the existence of non-permissive cells against FL. Our results also suggest that some molecules on target-cells other than the binding targets of SV-derived protein may participate in fusion between FL and cells.
Watabe
A
A
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. watabe@nihs.go.jp
Yamaguchi
T
T
Kawanishi
T
T
Uchida
E
E
Eguchi
A
A
Mizuguchi
H
H
Mayumi
T
T
Nakanishi
M
M
Hayakawa
T
T
D004167:Diphtheria Toxin / Q000494:pharmacology; D004337:Drug Carriers; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology*; D008081:Liposomes; D008561:Membrane Fusion; D009000:Monocytes / Q000502:physiology* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000494:pharmacology; D018108:Respirovirus / Q000502:physiology; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000502:physiology
D004167:Diphtheria Toxin; D004337:Drug Carriers; D008081:Liposomes; D010446:Peptide Fragments; D014764:Viral Proteins; C029795:diphtheria toxin fragment A