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In vivo targeting of cell death using a synthetic fluorescent molecular probe

机译:使用合成荧光分子探针在体内靶向细胞死亡

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摘要

A synthetic, near-infrared, fluorescent probe, named PSS-794 was assessed for its ability to detect cell death in two animal models. The molecular probe contains a zinc(II)-dipicolylamine (Zn2+-DPA) affinity ligand that selectively targets exposed phosphatidylserine on the surface of dead and dying cells. The first animal model used rats that were treated with dexamethasone to induce thymic atrophy. Ex vivo fluorescence imaging and histological analysis of excised organs showed thymus uptake of PSS-794 was four times higher than a control fluorophore that lacked the Zn2+-DPA affinity ligand. In addition, the presence of PSS-794 produced a delayed and higher build up of dead and dying cells in the rat thymus. The second animal model employed focal beam radiation to induce cell death in tumor-bearing rats. Whole-body and ex vivo imaging showed that the amount of PSS-794 in a radiation-treated tumor was almost twice that in a non-treated tumor. The results indicate that PSS-794 may be useful for preclinical optical detection of tumor cell death due to therapy.
机译:评估了一种名为PSS-794的合成,近红外荧光探针在两种动物模型中检测细胞死亡的能力。该分子探针包含锌(II)-二甲基吡啶胺(Zn 2 + -DPA)亲和配体,该配体选择性靶向死亡和垂死细胞表面上暴露的磷脂酰丝氨酸。第一个动物模型使用了地塞米松治疗的大鼠,诱发胸腺萎缩。切除器官的离体荧光成像和组织学分析显示,胸腺对PSS-794的摄取比缺乏Zn 2 + -DPA亲和配体的对照荧光团高四倍。另外,PSS-794的存在在大鼠胸腺中产生了延迟和较高的死细胞和垂死细胞堆积。第二种动物模型采用聚焦束辐射诱导荷瘤大鼠的细胞死亡。全身和离体成像显示,放射治疗的肿瘤中PSS-794的量几乎是未治疗的肿瘤中PSS-794的两倍。结果表明,PSS-794可用于临床前光学检测治疗引起的肿瘤细胞死亡。

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