Applied Cell Sciences Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran ; Research Center for Science and Technology in Medicine (RCSTiM), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
PLoS One. 2013 Nov 22;8(11):e79907. doi: 10.1371/journal.pone.0079907. eCollection 2013.
Using phages is a novel field of cancer therapy and phage nanobioparticles (NBPs) such as λ phage could be modified to deliver and express genetic cassettes into eukaryotic cells safely in contrast with animal viruses. Apoptin, a protein from chicken anemia virus (CAV) has the ability to specifically induce apoptosis only in carcinoma cells. We presented a safe method of breast tumor therapy via the apoptin expressing λ NBPs. Here, we constructed a λ ZAP-CMV-apoptin recombinant NBP and investigated the effectiveness of its apoptotic activity on BT-474, MDA-MB-361, SKBR-3, UACC-812 and ZR-75 cell lines that over-expressing her-2 marker. Apoptosis was evaluated via annexin-V fluorescent iso-thiocyanate/propidium iodide staining, flow-cytometric method and TUNEL assay. Transfection with NBPs carrying λ ZAP-CMV-apoptin significantly inhibited growth of all the breast carcinoma cell lines in vitro. Also nude mice model implanted BT-474 human breast tumor was successfully responded to the systemic and local injection of untargeted recombinant λ NBPs. The results presented here reveal important features of recombinant λ nanobioparticles to serve as safe delivery and expression platform for human cancer therapy.
利用噬菌体是癌症治疗的一个新领域,噬菌体纳米生物粒子(NBPs),如 λ 噬菌体,可以被修饰,以安全地将遗传盒递送到真核细胞中,这与动物病毒形成对比。凋亡蛋白,来自鸡贫血病毒(CAV)的一种蛋白质,具有特异性诱导仅在癌细胞中发生凋亡的能力。我们提出了一种通过表达凋亡蛋白的 λ NBPs 进行乳腺癌治疗的安全方法。在这里,我们构建了一个 λ ZAP-CMV-apoptin 重组 NBP,并研究了其在过度表达 her-2 标志物的 BT-474、MDA-MB-361、SKBR-3、UACC-812 和 ZR-75 细胞系中诱导凋亡活性的有效性。通过 Annexin-V 荧光异硫氰酸酯/碘化丙啶染色、流式细胞术和 TUNEL 检测评估凋亡。转染携带 λ ZAP-CMV-apoptin 的 NBPs 显著抑制了所有体外乳腺癌细胞系的生长。此外,裸鼠模型植入 BT-474 人乳腺癌对未靶向重组 λ NBPs 的全身和局部注射有反应。这里呈现的结果揭示了重组 λ 纳米生物粒子作为人类癌症治疗的安全递药和表达平台的重要特征。