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Bispecific T-cell engager (BiTE) immunotherapy of ovarian cancer based on MIL-88A MOF/MC gene delivery system
Applied Materials Today ( IF 8.3 ) Pub Date : 2020-06-10 , DOI: 10.1016/j.apmt.2020.100701
Jing Zhao , Danping Lu , Sergio Moya , Haoying Yan , Miaojuan Qiu , JunZong Chen , Xincheng Wang , Yang Li , Haobo Pan , Guochuang Chen , Guocheng Wang

Bispecific T-cell engager (BiTE) immunotherapy is a promising therapy for cancer treatment. However, the high cost and short life-time in vivo of the BiTE limit its wide clinical application. Here, we built for the first time a gene delivery system based on MIL-88A metal organic framework nanoparticles and minicricle DNA (MOF/MC) to realize high-efficient in vivo expression of anti-CD3/anti-EpCAM BiTE. X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) analysis verified that MC molecules were loaded onto MOF nanoparticles through metal-phosphate bonds and electrostatic interactions. It is found that intraperitoneal injection (i.p.) of MOF/MC suspensions showed good transfection performance in mice abdominal cavity with low toxicity. In an intraperitoneal xenograft mice model established using SKOV3 ovarian cells, i.p. injection of MOF/MC.BiTE significantly inhibited tumor growth and prolonged the average survival time of the mice. Overall, our study demonstrates a simple and highly efficient MOF-based gene delivery system holding promise for effective ovarian cancer immunotherapy.



中文翻译:

基于MIL-88A MOF / MC基因递送系统的卵巢癌双特异性T细胞接合剂(BiTE)免疫疗法

双特异性T细胞接合剂(BiTE)免疫疗法是一种有前途的癌症治疗方法。然而,BiTE的高成本和体内短寿命限制了其广泛的临床应用。在这里,我们首次构建了基于MIL-88A金属有机框架纳米颗粒和小分子DNA(MOF / MC)的基因递送系统,以实现高效体内CD3 /抗EpCAM BiTE的表达。X射线光电子能谱(XPS)和动态光散射(DLS)分析证实,MC分子通过金属磷酸盐键和静电相互作用被装载到MOF纳米颗粒上。发现腹膜内注射(ip)的MOF / MC悬浮液在小鼠腹腔中表现出良好的转染性能,且毒性低。在使用SKOV3卵巢细胞建立的腹膜内异种移植小鼠模型中,ip注射MOF / MC.BiTE可以显着抑制肿瘤的生长并延长小鼠的平均存活时间。总的来说,我们的研究表明,基于MOF的简单高效基因传递系统有望为有效的卵巢癌免疫疗法带来希望。

更新日期:2020-06-10
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