Synthesis and application of a non-viral gene delivery system for immunogene therapy of cancer
Synthesis and application of a non-viral gene delivery system for immunogene therapy of cancer
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DOI：
10.1016/j.jconrel.2005.09.024
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发表时间：
2005-12-05
影响因子：
10.8
通讯作者：
Anwer, K
中科院分区：
文献类型：
--
作者：
Fewell, JG;Matar, M;Anwer, K
介绍了一种新型脂质聚合物PEG-PEI-CHOL（PPC）的合成及基因传递应用。PPC由低分子量支链聚乙烯亚胺（PEI）与甲氧基聚乙二醇（PEG）和胆固醇（CHOL）官能团共价连接组成。PPC作为基因递送聚合物的潜在效用通过显示其与DNA形成稳定的纳米复合物、保护DNA免受DNA酶降解以及在实体瘤中在体外和体内介导基因转移的能力来评估。PEG/PEI/CHOL和氮与磷酸盐（聚合物/DNA）的比率针对PPC/DNA复合物的物理化学性质和基因递送效率进行优化。在将与PPC一起配制的鼠IL-12质粒（pmIL-12）施用到小鼠肿瘤中后，显示了聚合物的基因治疗应用，这导致肿瘤生长的显著抑制。pmIL-12/PPC的抑制作用在与特异性化疗剂组合时增强，证明pIL-12/PPC作为癌症治疗的辅助疗法的潜在有用性。(c)2005 Elsevier B. V.保留所有权利。
The synthesis and gene delivery application of a novel lipopolymer, PEG-PEI-CHOL (PPC), is described. PPC is composed of a low molecular weight branched polyethylenimine (PEI) covalently linked with functional groups methoxypolyethyleneglycol (PEG) and cholesterol (CHOL). The potential utility of PPC as a gene delivery polymer was evaluated by showing its ability to form stable nanocomplexes with DNA, protect DNA from degradation by DNase and mediate gene transfer in vitro and in vivo in solid tumors. The ratio of PEG/PEI/CHOL and nitrogen to phosphate (Polymer/DNA) was optimized for physicochemical properties and gene delivery efficiency of PPC/DNA complexes. The gene therapy application of the polymer was shown following administration of a murine IL-12 plasmid (pmIL-12) formulated with PPC into tumors in mice which resulted in significant inhibition of tumor growth. The inhibitory effects of pmIL-12/PPC were enhanced when combined with specific chemotherapeutic agents, demonstrating the potential usefulness of pIL-12/PPC as an adjuvant therapy for cancer treatment. (c) 2005 Elsevier B.V. All rights reserved.