Tumor targeting with surface-shielded ligand-polycation DNA complexes
Tumor targeting with surface-shielded ligand-polycation DNA complexes
复制标题
DOI：
10.1016/s0168-3659(01)00272-3
复制
发表时间：
2001-05-14
影响因子：
10.8
通讯作者：
Wagner, E
中科院分区：
文献类型：
--
作者：
Kircheis, R;Blessing, T;Wagner, E
将受体结合配体转铁蛋白（Tf）或表皮生长因子（EGF）掺入DNA/聚乙烯亚胺（PEI）复合物中，发现以受体依赖性方式增强基因转移到肿瘤细胞系中。在系统应用中，DNA复合物的表面电荷决定了基因转移的体内特性。将表面屏蔽的Tf-聚阳离子/DNA复合物施用到A/J小鼠的尾静脉中导致优先基因递送到远处生长的皮下Neuro 2a肿瘤中。相反，应用带正电荷的DNA/PEI复合物将基因转移主要引导至肺。实现了掩蔽配合物表面电荷的两种选择。在第一种情况下，通过用聚乙二醇（PEG）共价包被DNA/Tf-PEI复合物来获得屏蔽。或者，将足够的Tf蛋白掺入DNA复合物中导致电荷屏蔽，即使没有PEG化。在后一种情况下，使用较低分子量的聚阳离子（对于Tf-PEI复合物为25 kDa PEI，或对于AVET复合物为32 kDa聚赖氨酸）。(C)2001爱思唯尔科技有限公司。保留所有权利。
Incorporation of the receptor binding ligands transferrin (Tf) or epidermal growth factor (EGF) into DNA/polyethylenimine (PEI) complexes was found to enhance gene transfer into tumor cell lines in a receptor-dependent manner. In systemic applications, the surface charge of DNA complexes dominated the in vivo characteristics of gene transfer. Administration of surface-shielded Tf-polycation/DNA complexes into the tail vein of A/J mice resulted in preferential gene delivery into distantly growing subcutaneous Neuro2a tumors. In contrast, application of positively charged DNA/PEI complexes directed gene transfer primarily to the lung. Two alternatives of masking the surface charge of complexes were accomplished. In the first ease, shielding was obtained by covalently coating of DNA/Tf-PEI complexes with polyethylene glycol (PEG). Alternatively, incorporation of sufficient Tf protein into the DNA complexes resulted in charge shielding even without PEGylation. In the latter case lower-molecular weight polycations (25 kDa PEI for Tf-PEI complexes, or 32 kDa polylysine for AVET complexes) were used. (C) 2001 Elsevier Science B.V. All rights reserved.