Xu Chen, Hu Wenting, Zhang Na, Qi Yu, Nie Jing-Jun, Zhao Nana, Yu Bingran, Xu Fu-Jian
Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
Biomaterials. 2020 Jul;248:120031. doi: 10.1016/j.biomaterials.2020.120031. Epub 2020 Apr 8.
Multimodal therapy has been continuously explored for different diseases. Photodynamic/gene combined therapy is a promising treatment strategy of tumor. However, the limitation of traditional chemical photosensitizer and the asynchronism of the two therapies restrict the development of this technology. Herein, one genetically multimodal treatment nanosystem (HES@PGEA/pKR-p53), composed of biocompatible hydroxyethyl starch (HES), low-toxic β-cyclodextrin-based ethanolamine-functionalized poly(glycidyl methacrylate) (CD-PGEA) and combined plasmid pKR-p53, is structurally designed based on host-guest assembly and electrostatic complexing. Supramolecular assembled HES@PGEA exhibits low cytotoxicity, excellent cellular internalization and enhanced gene transfection efficiency. With the delivery of pKR-p53, p53 and KillerRed proteins could be expressed simultaneously in the same tumor cell for p53-mediated apoptosis therapy and photodynamic therapy (PDT), where the synergistic effect of KillerRed and p53 proteins is achieved. Compared with single therapy, HES@PGEA/pKR-p53 shows more remarkable antitumor effects in the 4T1 tumor model.
针对不同疾病，人们一直在不断探索多模态疗法。光动力/基因联合疗法是一种很有前景的肿瘤治疗策略。然而，传统化学光敏剂的局限性以及两种疗法的不同步性限制了该技术的发展。在此，一种基于主客体组装和静电络合结构设计的基因多模态治疗纳米系统（HES@PGEA/pKR-p53）被构建出来，它由生物相容性羟乙基淀粉（HES）、低毒的基于β-环糊精的乙醇胺功能化聚甲基丙烯酸缩水甘油酯（CD-PGEA）和联合质粒pKR-p53组成。超分子组装的HES@PGEA表现出低细胞毒性、优异的细胞内化能力和增强的基因转染效率。随着pKR-p53的递送，p53和KillerRed蛋白可在同一肿瘤细胞中同时表达，用于p53介导的凋亡疗法和光动力疗法（PDT），实现KillerRed和p53蛋白的协同效应。与单一疗法相比，HES@PGEA/pKR-p53在4T1肿瘤模型中显示出更显著的抗肿瘤效果。
