title: Cell derived liposomes expressing CCR5 as a new targeted drug-delivery system for HIV infected cells.
abstract: Anti-retroviral-therapies against HIV/AIDS focus on inhibiting viral growth and may slow AIDS progression, but not cure the disease. Here we describe an approach to treat HIV as a cellular pathology by targeting cell derived liposomes against HIV-infected cells. Cell-derived-liposomes were prepared from the cytoplasmatic membranes of cells expressing CCR5, the human receptor for gp120, that is found on the surface of virions and HIV-infected cells. The specific targeting and cytotoxicity of the cell-derived liposomes towards gp120-expressing cells were studied. Cell-derived liposomes exhibited unilamellar morphology and were found to be of 100-200 nm in diameter. Moreover, CCR5 that was expressed on the surface of the cell-derived liposomes was biologically active and correctly oriented. Cell-derived liposomes incubated with HIV-infected model cells exhibited significant and specific targeting to those gp120-expressing cells. To demonstrate the system efficacy, EDTA was selected as liposomal encapsulate and was shown to cause high cytotoxic effect when introduced into the cell cytoplasm. Finally, cell-derived liposomes containing EDTA led to a 60% reduction in the viability of gp120-expressing cells compared to no effect on control cells that do not express gp120. These results demonstrate the specific targeting and cytotoxic effect of CCR5-conjugated cell-derived liposomes towards gp120-expressing HIV model cells, suggesting for a potential new therapeutic approach.
authors.affiliation: Faculty of Biotechnology and Food Engineering, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Bronshtein
authors.forename: Naama
authors.initials: N
authors.lastname: Toledano
authors.forename: Dganit
authors.initials: D
authors.lastname: Danino
authors.forename: Shimon
authors.initials: S
authors.lastname: Pollack
authors.forename: Marcelle
authors.initials: M
authors.lastname: Machluf
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000378:metabolism; D002417:Cattle; D018920:Coculture Techniques; D006224:Cricetinae; D016503:Drug Delivery Systems / Q000379:methods*; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008081:Liposomes; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D008081:Liposomes; D019713:Receptors, CCR5; C514793:gp120 protein, Human immunodeficiency virus 1