Targeted light-inactivation of the Ki-67 protein using theranostic liposomes leads to death of proliferating cells
Targeted light-inactivation of the Ki-67 protein using theranostic liposomes leads to death of proliferating cells
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使用治疗诊断脂质体对 Ki-67 蛋白进行靶向光灭活导致增殖细胞死亡
DOI：
10.1117/12.843850
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Hasan T
中科院分区：
文献类型：
--
作者：
Rahmanzadeh R;Gerdes J;Hasan T
纳米医学开始影响几种疾病的治疗，目前的研究工作包括开发集成的纳米结构（治疗诊断学），除了在细胞内递送大分子外，还可用作成像和治疗的探针。在癌症中，对于具有高特异性和低全身毒性的有效替代治疗存在重要的未满足的需求。这可以通过以减少的有效药物剂量靶向与癌细胞相关的关键分子标志物来实现。在这里，我们展示了一种创新的原理验证方法，通过使用基于纳米技术的光动力疗法（PDT）灭活与细胞增殖相关的蛋白质，即核Ki-67蛋白（pKi-67），有效杀死增殖的卵巢癌细胞。针对pKi-67的抗体被广泛用作肿瘤诊断的预后工具。在这项工作中，抗pKi-67抗体首先与异硫氰酸荧光素（FITC）结合，然后封装在脂质体内。将OVCAR-5卵巢癌细胞与这些脂质体孵育后，共聚焦显微镜证实抗体定位于细胞的核仁。用488 nm激光照射导致细胞活力显著丧失。在融合的人肺成纤维细胞（MRC-5）中证明了该方法对pKi-67阳性细胞的特异性，其中仅少量细胞群体对pKi-67染色呈阳性，并且仅观察到极轻微的细胞死亡。综上所述，我们的研究结果表明，pKi-67靶向与纳米平台是一个有吸引力的治疗靶点在癌症治疗。
Nanomedicine is beginning to impact the treatment of several diseases and current research efforts include development of integrated nano-constructs (theranostics) which serve as probes for imaging and therapy in addition to delivering macromolecules intracellularly. In cancer, there is a vital unmet need for effective alternative treatments with high specificity and low systemic toxicity. This can be achieved by targeting key molecular markers associated with cancer cells with reduced effective drug doses. Here, we show an innovative proof-of-principle approach for efficient killing of proliferating ovarian cancer cells by inactivating a protein associated with cell proliferation namely, the nuclear Ki-67 protein (pKi-67), using nanotechnology-based photodynamic therapy (PDT). Antibodies against pKi-67 are widely used as prognostic tools for tumor diagnosis. In this work, anti pKi-67 antibodies were first conjugated to fluorescein isothiocyanate (FITC) and then encapsulated inside liposomes. After incubation of OVCAR-5 ovarian cancer cells with these liposomes, confocal microscopy confirmed the localization of the antibodies to the nucleoli of the cells. Irradiation with a 488 nm laser led to a significant loss of cell viability. The specificity of this approach for pKi-67 positive cells was demonstrated in confluent human lung fibroblasts (MRC-5) where only a small population of cells stain positive for pKi-67 and only minimal cell death was observed. Taken together, our findings suggest that pKi-67 targeted with nano-platform is an attractive therapeutic target in cancer therapy.
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影响因子：
3
作者：
R. Gomory
通讯作者：
R. Gomory