科研之友
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摘要
For active cell targeting, viruses frequently capitalize on dual-receptor binding. With the intention to mimic this natural process, a dual peptide-based approach for targeting cancer cells was evaluated. For this purpose, sequence-defined pDNA binding oligo (ethane amino) amides containing a PEG chain with a peptidic targeting ligand at its distal end were applied. Integrin receptor-directed cyclic peptide cRGDfk, transferrin receptor-addressing peptide B6, and epidermal growth factor receptor-targeting peptide GE11 were used in the study in DU145 prostate cancer cells that express all three receptors. Dual-receptor targeted pDNA polyplexes were designed by combining two of the above ligands at various ratios, in order to find an optimal ligand combination. Two polycation/pDNA ratios of nitrogen/phosphate (N/P) 6 and 12 were tested. Dual targeting effects were most pronounced at the lower N/P ratio and found for all three combinations. Cell binding studies and pDNA transfections revealed GE11 plus B6 as the most potent combination. In general, a good correlation of cell binding with gene transfer was observed. Interestingly, GE11 peptide-based polyplexes-mediated bimodal cell association profiles. In contrast, B6 ligand, cRGD ligand, and dual-targeted polyplexes triggered more homogenous monomodal cell binding characteristics.
- 出版日期2015-2
- 单位四川大学
