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.

对于不同的疾病，多模式疗法已被不断探索。光动力/基因联合治疗是一种有希望的肿瘤治疗策略。然而，传统化学光敏剂的局限性和两种疗法的异步性限制了该技术的发展。在这里，一个基因多模式治疗纳米系统（HES @ PGEA / pKR-p53），由生物相容性羟乙基淀粉（HES），低毒性基于β-环糊精的乙醇胺官能化聚甲基丙烯酸缩水甘油酯（CD-PGEA）组成pKR-p53在结构上是基于主客体组装和静电复合的。超分子组装的HES @ PGEA具有低细胞毒性，优异的细胞内在化和增强的基因转染效率。随着pKR-p53的交付，p53和KillerRed蛋白可以在同一肿瘤细胞中同时表达，以进行p53介导的细胞凋亡治疗和光动力疗法（PDT），从而实现KillerRed和p53蛋白的协同作用。与单一疗法相比，HES @ PGEA / pKR-p53在4T1肿瘤模型中显示出更显着的抗肿瘤作用。