Mannosylated Cationic Copolymers for Gene Delivery to Macrophages
| Autor: | Natalia L. Klyachko, Elena V. Batrakova, Zigang Yang, Anton V Lopukhov, Marina Sokolsky-Papkov, Matthew J. Haney, Alexander V. Kabanov, Tatiana K. Bronich |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Polymers and Plastics Light Polymers Genetic enhancement Mannose Succinimides Bioengineering 02 engineering and technology Gene delivery 010402 general chemistry Ligands Microscopy Atomic Force 01 natural sciences Article Polyethylene Glycols Biomaterials chemistry.chemical_compound Mice C-type lectin Cations Materials Chemistry Animals Humans Scattering Radiation Polylysine Cytotoxicity Aspartame Macrophages Gene Transfer Techniques Transfection DNA Fibroblasts 021001 nanoscience & nanotechnology Molecular biology Polyelectrolytes 0104 chemical sciences Cross-Linking Reagents chemistry Cell culture Chromatography Gel NIH 3T3 Cells 0210 nano-technology Mannose receptor Mannose Receptor Biotechnology Plasmids |
| Zdroj: | Macromol Biosci |
| Popis: | Macrophages are desirable targets for gene therapy of cancer and other diseases. Cationic diblock copolymers of polyethylene glycol (PEG) and poly-L-lysine (PLL) or poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (pAsp(DET)) are synthesized and used to form polyplexes with a plasmid DNA (pDNA) that are decorated with mannose moieties, serving as the targeting ligands for the C type lectin receptors displayed at the surface of macrophages. The PEG-b-PLL copolymers are known for its cytotoxicity, so PEG-b-PLL-based polyplexes are cross-linked using reducible reagent dithiobis(succinimidyl propionate) (DSP). The cross-linked polyplexes display low toxicity to both mouse embryonic fibroblasts NIH/3T3 cell line and mouse bone marrow-derived macrophages (BMMΦ). In macrophages mannose-decorated polyplexes demonstrate an ≈8 times higher transfection efficiency. The cross-linking of the polyplexes decrease the toxicity, but the transfection enhancement is moderate. The PEG-b-pAsp(DET) copolymers display low toxicity with respect to the IC-21 murine macrophage cell line and are used for the production of non-cross-linked pDNA-contained polyplexes. The obtained mannose modified polyplexes exhibit ca. 500-times greater transfection activity in IC-21 macrophages compared to the mannose-free polyplexes. This result greatly exceeds the targeting gene transfer effects previously described using mannose receptor targeted non-viral gene delivery systems. These results suggest that Man-PEG-b-pAsp(DET)/pDNA polyplex is a potential vector for immune cells-based gene therapy. |
| Databáze: | OpenAIRE |
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