Genetically multimodal therapy mediated by one polysaccharides-based supramolecular nanosystem
Genetically multimodal therapy mediated by one polysaccharides-based supramolecular nanosystem
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一种基于多糖的超分子纳米系统介导的遗传多模式疗法
DOI：
10.1016/j.biomaterials.2020.120031
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发表时间：
2020-07-01
期刊：
影响因子：
14
通讯作者：
Xu, Fu-Jian
中科院分区：
文献类型：
--
作者：
Xu, Chen;Hu, Wenting;Xu, Fu-Jian
针对不同疾病的多模式治疗一直在不断探索。光动力/基因联合治疗是一种很有前途的肿瘤治疗策略。然而，传统化学光敏剂的局限性和两种治疗方法的不同步制约了该技术的发展。本论文基于主客体组装和静电络合的方法，构建了一种由生物相容羟乙基淀粉(HES)、低毒β-环糊精乙醇胺功能化的聚甲基丙烯酸缩水甘油酯(CD-PGEA)和重组质粒PKR-P53组成的基因多模式治疗纳米系统(HES@PGEA/PKR-P53)。超分子组装的HES@PGEA具有低的细胞毒性、良好的细胞内化能力和较高的基因转染率。在P53介导的细胞凋亡治疗和光动力治疗(PDT)中，PKR-P53、P53和KillerRed蛋白可以在同一肿瘤细胞中同时表达，从而达到KillerRed和P53蛋白的协同作用。与单一治疗相比，HES@PGEA/PKR-P53在4T1肿瘤模型中显示出更显著的抗肿瘤作用。
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 photo-sensitizer 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 beta-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.