Calcium phosphate nanoneedle based gene delivery system for cancer genetic immunotherapy
Calcium phosphate nanoneedle based gene delivery system for cancer genetic immunotherapy
复制标题
基于磷酸钙纳米针的基因递送系统用于癌症遗传免疫治疗
DOI：
10.1016/j.biomaterials.2020.120072
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发表时间：
2020
期刊：
影响因子：
14
通讯作者：
Chen Zhi-Ying
中科院分区：
文献类型：
--
作者：
Zhao Jing;Chen Guochuang;Pang Xiaojuan;Zhang Peifa;Hou Xiaohu;Chen Ping;Xie Yi-Wu;He Cheng-Yi;Wang Zhiyong;Chen Zhi-Ying
卵巢癌已成为最常见的妇科癌症之一，死亡率高。然而，常规手术联合化疗难以达到理想的治疗效果。虽然基因免疫疗法被应用于主动免疫应答，但缺乏有效的体内基因传递技术仍然是临床应用的障碍。为了克服这些问题，构建了一种编码人源抗epcam /CD3双特异性抗体（BsAbEPH）的小圆DNA载体。此外，制备了不同形状的磷酸钙（CaPO）生物材料。具体来说，capo纳米针介导的“细胞穿孔”转染技术在腹腔中实现了高水平的基因表达。在人卵巢癌细胞系SKOV3腹腔异种移植模型中，表达bsabephh的capo -纳米针/微环DNA系统显著延缓肿瘤生长，延长小鼠寿命，但毒性有限。该系统可以制成现成的、易于使用的产品。因此，基于capo纳米针的非病毒基因传递技术具有很大的临床应用潜力。
Ovarian cancer has become one of the most common gynecological cancers with a high mortality. However, conventional surgery together with combination chemotherapy is difficult to achieve ideal therapeutic effect. Although genetic immunotherapy is applied to active immune responses against cancer, the absence of efficient in vivo gene delivery technique is still an obstacle in clinical application. To overcome these problems, a minicircle DNA vector encoding humanized anti-EpCAM/CD3 bispecific antibody (BsAbEPH) has been constructed. Moreover, different shapes of calcium phosphate (CaPO) biomaterials were prepared. Specifically, the CaPO-nanoneedle-mediated “cell perforation” transfection technology achieves high levels of gene expression in peritoneal cavity. In an intraperitoneal xenograft model with human ovarian cancer cell line SKOV3, the CaPO-nanoneedle/minicircle DNA system expressed BsAbEPHresulted in significant retardation of cancer growth and extension of mouse life-span with limited toxicity. And this system can be made as off-the-shelf and easy-to-use products. Therefore, CaPO-nanoneedle based non-viral gene delivery technology will have great potential in clinical application.