J Control Release, 2012, 163(2):211-219

Subcellular trafficking and transfection efficacy of polyethylenimine- polyethylene glycol polyplex nanoparticles with a ligand to melanocortin receptor-1

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. © 2012 Elsevier B.V.

Durymanov MO, Beletkaia EA, Ulasov AV, Khramtsov YV, Trusov GA, Rodichenko NS, Slastnikova TA, Vinogradova TV, Uspenskaya NY, Kopantsev EP, Rosenkranz AA, Sverdlov ED, Sobolev AS

IBCH: 4857
Ссылка на статью в журнале: http://linkinghub.elsevier.com/retrieve/pii/S0168365912006499
Кол-во цитирований на 12.2023: 36
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