Faculty of Biotechnology and Food Engineering, Technion, Israel Institute of Technology, Haifa, Israel.
J Control Release. 2011 Apr 30;151(2):139-48. doi: 10.1016/j.jconrel.2011.02.023. Epub 2011 Feb 26.
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.
抗逆转录病毒疗法针对 HIV/AIDS 主要集中在抑制病毒生长，从而可能减缓艾滋病的进展，但不能治愈该疾病。在这里，我们描述了一种通过靶向细胞衍生的脂质体来治疗 HIV 的方法，该脂质体针对感染 HIV 的细胞。细胞衍生的脂质体是从表达 CCR5 的细胞质膜中制备的，CCR5 是 HIV 病毒和感染细胞表面 gp120 的人类受体。研究了细胞衍生的脂质体对表达 gp120 的细胞的特异性靶向和细胞毒性。细胞衍生的脂质体具有单分子层形态，直径为 100-200nm。此外，细胞衍生的脂质体表面表达的 CCR5 具有生物活性且正确取向。用 HIV 感染的模型细胞孵育的细胞衍生脂质体表现出对那些表达 gp120 的细胞的显著和特异性靶向。为了证明该系统的功效，选择 EDTA 作为脂质体包封物，并表明当引入细胞细胞质时会引起高细胞毒性效应。最后，与不表达 gp120 的对照细胞相比，含有 EDTA 的细胞衍生脂质体导致表达 gp120 的细胞活力降低了 60%。这些结果表明，CCR5 缀合的细胞衍生脂质体对表达 gp120 的 HIV 模型细胞具有特异性靶向和细胞毒性作用，提示了一种新的潜在治疗方法。
