Polyplex Micelles from Triblock Copolymers Composed of Tandemly Aligned Segments with Biocompatible, Endosomal Escaping, and DNA-Condensing Functions for Systemic Gene Delivery to Pancreatic Tumor Tissue
Polyplex Micelles from Triblock Copolymers Composed of Tandemly Aligned Segments with Biocompatible, Endosomal Escaping, and DNA-Condensing Functions for Systemic Gene Delivery to Pancreatic Tumor Tissue
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DOI：
10.1007/s11095-008-9720-2
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发表时间：
2008-12-01
影响因子：
3.7
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
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作者：
Miyata, Kanjiro;Oba, Makoto;Kataoka, Kazunori
对于胰腺肿瘤组织的系统性基因递送，我们从三个串联排列的组分制备了具有生物相容性、有效内体逃逸和pDNA缩合功能的三层复合物胶束;聚聚乙二醇（PEG），一种聚具有1，2-二氨基乙烷部分的（异丙酰胺）衍生物分别通过动态光散射（DLS）和荧光素酶测定法测定复合物胶束的大小和体外转染效率。通过增强肿瘤组织中的绿色荧光蛋白（EGFP）表达来评价聚合物胶束的系统性基因递送，聚合物胶束的尺寸约为80 nm，并且具有比作为对照的二嵌段共聚物高一个数量级的体外转染效率。借助转化生长因子（TGF）-β I型受体（T β R-1）抑制剂，其增强大分子药物在肿瘤组织中的积累，来自三嵌段共聚物的复合物胶束在胰腺肿瘤（BxPC 3）组织中显示出显著的EGFP表达，主要分布在基质区，包括血管内皮细胞和成纤维细胞。证实了层状复合物胶束是通过全身给药对皮下植入的胰腺肿瘤组织有效的基因递送系统。
For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine).The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues.The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-beta type I receptor (T beta R-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts.The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.