Han Xiao-Jian, Wei Yong-Fang, Wan Yu-Ying, Jiang Li-Ping, Zhang Jian-Feng, Xin Hong-Bo
Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, P.R. China.
Int J Mol Med. 2014 Nov;34(5):1225-32. doi: 10.3892/ijmm.2014.1922. Epub 2014 Sep 4.
Liposomes as targeted drug delivery systems are an emerging strategy in the treatment of cancer to selectively target tumors or genes. In this study, we generated the recombinant protein, EC1-GLuc, by fusing the EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc). The purified EC1-GLuc was conjugated with a nickel-chelating liposome to construct the EC1-GLuc-liposome. In vitro experiments revealed that the EC1-GLuc-liposome selectively targeted and internalized into ErbB2-overexpressing SKOv3 cells for bioluminescence imaging. A cell-impermeable fluorescence dye (HPTS) encapsulated in the EC-GLuc-liposome was efficiently delivered into the SKOv3 cells. In addition, the EC1-GLuc-liposome also targeted metastatic SKOv3 tumors for bioluminescence imaging and effectively delivered HPTS into metastatic tumors in vivo. Therefore, the present study demonstrates the novel EC1-GLuc-liposome to be an effective theranostic system for monitoring and treating ErbB2-overexpressing metastatic ovarian carcinoma through a combination of targeted molecular imaging and DDS.
脂质体作为靶向给药系统,是癌症治疗中一种新兴的策略,用于选择性地靶向肿瘤或基因。在本研究中,我们通过将ErbB2的人工配体EC1肽与高斯荧光素酶(GLuc)融合,生成了重组蛋白EC1-GLuc。将纯化的EC1-GLuc与镍螯合脂质体偶联,构建了EC1-GLuc-脂质体。体外实验表明,EC1-GLuc-脂质体可选择性地靶向并内化到过表达ErbB2的SKOv3细胞中,用于生物发光成像。包裹在EC-GLuc-脂质体中的细胞不可渗透荧光染料(HPTS)被有效地递送至SKOv3细胞中。此外,EC1-GLuc-脂质体还可靶向转移性SKOv3肿瘤进行生物发光成像,并在体内有效地将HPTS递送至转移性肿瘤中。因此,本研究证明新型EC1-GLuc-脂质体是一种有效的治疗诊断系统,可通过靶向分子成像和药物递送系统的组合来监测和治疗过表达ErbB2的转移性卵巢癌。