1] Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA [2].
Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI 02881, USA.
Sci Rep. 2013 Dec 20;3:3560. doi: 10.1038/srep03560.
Proper balance of ions in intracellular and extracellular space is the key for normal cell functioning. Changes in the conductance of membranes for ions will lead to cell death. One of the main differences between normal and cancerous cells is the low extracellular pHe and the reverse pH gradient: intracellular pHi is higher than extracellular pHe. We report here pH-selective transfer of nano-pores to cancer cells for the dis-regulation of balance of monovalent cations to induce cell death at mildly acidic pHe as it is in most solid tumors. Our approach is based on the pH-sensitive fusion of cellular membrane with the liposomes containing gramicidin A forming cation-conductive β-helix in the membrane. Fusion is promoted only at low extracellular pH by the pH (Low) Insertion Peptide (pHLIP®) attached to the liposomes. Gramicidin channels inserted into the cancer cells open flux of protons into the cytoplasm and disrupt balance of other monovalent cations, which induces cell apoptosis.
细胞内外离子的适当平衡是正常细胞功能的关键。离子膜电导率的变化会导致细胞死亡。正常细胞和癌细胞的主要区别之一是细胞外 pH 值低，pH 梯度相反：细胞内 pH 值高于细胞外 pH 值。我们在这里报告了纳米孔对癌细胞的 pH 选择性转移，以在轻度酸性 pH 值下（如大多数实体瘤中那样）调节单价阳离子平衡，从而诱导细胞死亡。我们的方法基于细胞膜与含有革兰氏菌素 A 的脂质体融合的 pH 敏感性，在膜中形成阳离子传导的 β-螺旋。只有在 pH 值较低的情况下，通过连接到脂质体上的 pH（低）插入肽（pHLIP®）才能促进融合。插入癌细胞的革兰氏菌素通道将质子流入细胞质，并破坏其他单价阳离子的平衡，从而诱导细胞凋亡。
