Subcellular trafficking and transfection efficacy of polyethylenimine-polyethylene glycol polyplex nanoparticles with a ligand to melanocortin receptor-1
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- 作者：Mikhail O. Durymanov ; Elena A. Beletkaia ; Alexey V. Ulasov ; Yuri V. Khramtsov ; Georgiy A. Trusov ; Nikita S. Rodichenko ; Tatiana A. Slastnikova ; Tatiana V. Vinogradova ; Natalia Y. Uspenskaya ; Eugene P. Kopantsev ; Andrey A. Rosenkranz ; Eugene D. Sverdlov ; Alex ; er S. Sobolev
- 关键词：Polyethylenimine ; Polyethylene glycol ; Polyplexes ; Melanocortin receptor-1 ; Intracellular trafficking ; Transfection
- 刊名：Journal of Controlled Release
- 出版年：2012
- 出版时间：28 October, 2012
- 年：2012
- 卷：163
- 期：2
- 页码：211-219
- 全文大小：1054 K
文摘
We have synthesized and investigated properties of new PEI-PEG-based polyplexes containing MC1SP-peptide, a ligand specific for melanocortin receptor-1 (targeted polyplexes), and control polyplexes without this ligand peptide (non-targeted polyplexes). The targeted polyplexes demonstrated receptor-mediated transfection of Cloudman S91 (clone M-3) murine melanoma cells that was more efficient than with the non-targeted ones. Transfection with the targeted polyplexes was inhibited by chlorpromazine, an inhibitor of the clathrin-mediated endocytosis pathway, and, to a lesser extent, by filipin III or nystatin, inhibitors of the lipid-raft endocytosis pathway, whereas transfection with the non-targeted polyplexes was inhibited mainly by nystatin or filipin III. The targeted polyplexes caused significantly higher in vivo transfection of melanoma tumor cells after intratumoral administration compared to the non-targeted control. The targeted polyplexes carrying the HSVtk gene, after ganciclovir administration, more efficiently inhibited melanoma tumor growth and prolonged the lifespan of DBA/2 tumor-bearing mice compared to the non-targeted ones. Packed targeted polyplexes appeared and accumulated in the melanoma cells 6 h earlier than the non-targeted ones. The targeted polyplexes enter into the nuclei of the melanoma cells more rapidly than the non-targeted control, and this difference may also be attributed to processes of receptor-mediated endocytosis. We believe that these data may be useful for the optimization of polyplex systems.