Tumor targeting with surface-shielded ligand-polycation DNA complexes

被引:128
作者
Kircheis, R
Blessing, T
Brunner, S
Wightman, L
Wagner, E
机构
[1] Boehringer Ingelheim Austria, A-1121 Vienna, Austria
[2] Univ Vienna, Bioctr, Inst Med Biochem, A-1030 Vienna, Austria
基金
奥地利科学基金会;
关键词
DNA transfection; EGF; polyethylenimine; receptor-mediated gene transfer; transferrin;
D O I
10.1016/S0168-3659(01)00272-3
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:165 / 170
页数:6
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