The targeted co-delivery of DNA and doxorubicin to tumor cells via multifunctional PEI-PEG based nanoparticles
The targeted co-delivery of DNA and doxorubicin to tumor cells via multifunctional PEI-PEG based nanoparticles
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DOI：
10.1016/j.biomaterials.2012.12.038
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发表时间：
2013-03-01
期刊：
影响因子：
14
通讯作者：
Zhang, Na
中科院分区：
文献类型：
--
作者：
Liu, Chunxi;Liu, Fengxi;Zhang, Na
核酸和化学治疗剂的共递送具有通过其协同效应有效治疗人类疾病的潜力。纳米级的可活化治疗工具是用于组合治疗的合适平台。在这项研究中，我们开发了一个多功能的纳米级传递系统，同时集成了被动和主动肿瘤靶向，细胞膜转位，pH触发的药物释放和共传递策略。通过在聚乙二醇（PEG）末端偶联达特，合成了聚乙烯亚胺（PEI）-PEG共聚物。PEI的功能性氨基用于通过pH敏感性腙键化学缀合多柔比星（DOX）。同时，阳离子PEI骨架可以将DNA复合到DOX负载的TAT修饰的聚离子复合物胶束（NPIC）中。为实现对肿瘤血管内皮细胞和肿瘤细胞的主动或被动双重靶向作用，将磺胺甲基嘧啶（SA）-PEG-NGR静电吸附于NPIC表面，构建了具有NGR功能的病毒模拟壳，制备了DOX靶向PIC胶束（TPIC）。建立多功能纳米给药系统，通过基因治疗与化疗的协同作用，全面提高肿瘤治疗的疗效。因此，该系统被证明是一种有前途的载体，用于DNA和DOX的共递送，导致基因转染的效率和体外抗肿瘤活性。(C)2013爱思唯尔有限公司保留所有权利。
Co-delivery of nucleic acids and chemotherapeutics has a potential to efficaciously treat human diseases via their synergetic effects. Activable therapeutic tools at the nanoscale are suitable platforms for combination therapy. In this study, we have developed a multifunctional nanoscaled delivery system simultaneously integrated with passive and active tumor targeting, cell membrane translocation, pH-triggered drug release and co-delivery strategies. Poly (ethyleneimine) (PEI)-polyethylene glycol (PEG) copolymer was synthesized with coupling TAT to the distal end of PEG for membrane activity. The functional amino group of PEI was used to chemically conjugate doxorubicin (DOX) via a pH-sensitive hydrazone linkage. Meanwhile, the cationic PEI backbone could complex DNA to DOX loaded-TAT modified polyion complex micelles (NPIC). To achieve double targeting effect to tumor vascular endothelial cells and tumor cells either by active or passive targeting, a virus mimetic shell functioned with NGR was conferred by electrostatic adsorption of sulfamerazine (SA)-PEG-NGR on the surface of NPIC to obtain DOX loaded targeted PIC micelles (TPIC). The multifunctional nanoscaled delivery system was established to comprehensively improve the efficacy of cancer therapy through the synergistic effect of gene therapy with chemotherapy. Consequently, the system was shown to be a promising carrier for the co-delivery of DNA and DOX, leading to the efficiency of gene transfection and anti-tumor activity in vitro. (C) 2013 Elsevier Ltd. All rights reserved.