pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo.

pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo.
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DOI:
10.1021/cb500388m
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发表时间:
2014-11-21
影响因子:
4
通讯作者:
Engelman, Donald M.
Engelman, Donald M.
中科院分区:
生物学2区
文献类型:
--
作者:
Katabadzhak, Alexander G.;An, Ming;Yao, Lan;Langenbacher, Rachel;Moshnikova, Anna;Adochite, Ramona-Cosmina;Andreev, Oleg A.;Reshetnyak, Yana K.;Engelman, Donald M.

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我们已经开发了一种改进的工具,通过报告跨膜螺旋的插入来成像酸性肿瘤:pHLIP-FIRE(pHLIP-Fluorescence Insertion REporter)。在酸性组织中,如肿瘤,pHLIP家族中的肽作为α-螺旋插入细胞膜。pHLIP-FIRE肽的细胞插入末端具有荧光团-荧光团或荧光团-猝灭剂对。在插入细胞内的还原环境后,通过二硫键裂解释放成对成员,导致探针去淬灭。因此,pHLIP-FIRE探针的荧光在靶组织中的细胞插入时增强,但在其他地方由于淬灭而被抑制。在携带乳腺肿瘤的小鼠中的靶向研究显示pHLIP-FIRE的强信号传导,对比度指数为1017,表明(i)pHLIP插入的直接成像和(ii)体内货物易位。成像和靶向货物输送应各自具有临床应用。
We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE peptide has a fluorophore–fluorophore or fluorophore–quencher pair. A pair member is released by disulfide cleavage after insertion into the reducing environment inside a cell, resulting in dequenching of the probe. Thus, the fluorescence of the pHLIP-FIRE probe is enhanced upon cell-insertion in the targeted tissues but is suppressed elsewhere due to quenching. Targeting studies in mice bearing breast tumors show strong signaling by pHLIP-FIRE, with a contrast index of ∼17, demonstrating (i) direct imaging of pHLIP insertion and (ii) cargo translocation in vivo. Imaging and targeted cargo delivery should each have clinical applications.
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