Cell derived liposomes expressing CCR5 as a new targeted drug-delivery system for HIV infected cells

TY - JOUR

T1 - Cell derived liposomes expressing CCR5 as a new targeted drug-delivery system for HIV infected cells

AU - Bronshtein, Tomer

AU - Toledano, Naama

AU - Danino, Dganit

AU - Pollack, Shimon

AU - MacHluf, Marcelle

PY - 2011/4/30

Y1 - 2011/4/30

N2 - 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.

AB - 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.

KW - AIDS

KW - CCR5

KW - Cell-derived

KW - EDTA

KW - HIV

KW - Liposome

UR - http://www.scopus.com/inward/record.url?scp=79956089145&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2011.02.023

DO - 10.1016/j.jconrel.2011.02.023

M3 - 文章

C2 - 21362450

AN - SCOPUS:79956089145

SN - 0168-3659

VL - 151

SP - 139

EP - 148

JO - Journal of Controlled Release

JF - Journal of Controlled Release

IS - 2

ER -