دورية أكاديمية
Mannosylated Cationic Copolymers for Gene Delivery to Macrophages.
| العنوان: | Mannosylated Cationic Copolymers for Gene Delivery to Macrophages. |
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| المؤلفون: | Lopukhov AV; Laboratory for Chemical Design of Bionanomaterials, Faculty of Chemistry, M. V. Lomonosov Moscow State University, 1 Leninskie Gory, Moscow, 117234, Russia., Yang Z; Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, NE, 68198, USA., Haney MJ; Division of Pharmacoengineering and Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, 125 Mason Farm Road, Chapel Hill, NC, 27599, USA., Bronich TK; Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, NE, 68198, USA., Sokolsky-Papkov M; Division of Pharmacoengineering and Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, 125 Mason Farm Road, Chapel Hill, NC, 27599, USA., Batrakova EV; Division of Pharmacoengineering and Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, 125 Mason Farm Road, Chapel Hill, NC, 27599, USA., Klyachko NL; Laboratory for Chemical Design of Bionanomaterials, Faculty of Chemistry, M. V. Lomonosov Moscow State University, 1 Leninskie Gory, Moscow, 117234, Russia.; Division of Pharmacoengineering and Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, 125 Mason Farm Road, Chapel Hill, NC, 27599, USA., Kabanov AV; Laboratory for Chemical Design of Bionanomaterials, Faculty of Chemistry, M. V. Lomonosov Moscow State University, 1 Leninskie Gory, Moscow, 117234, Russia.; Division of Pharmacoengineering and Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina, 125 Mason Farm Road, Chapel Hill, NC, 27599, USA. |
| المصدر: | Macromolecular bioscience [Macromol Biosci] 2021 Apr; Vol. 21 (4), pp. e2000371. Date of Electronic Publication: 2021 Feb 22. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101135941 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1616-5195 (Electronic) Linking ISSN: 16165187 NLM ISO Abbreviation: Macromol Biosci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Weinheim, Germany : Wiley-VCH, c2001- |
| مواضيع طبية MeSH: | Cations* , Gene Transfer Techniques*, Macrophages/*metabolism , Mannose/*chemistry , Polyethylene Glycols/*chemistry , Polylysine/*chemistry , Polymers/*chemistry, Animals ; Aspartame/chemistry ; Chromatography, Gel ; Cross-Linking Reagents/chemistry ; DNA/chemistry ; Fibroblasts/metabolism ; Humans ; Ligands ; Light ; Magnetic Resonance Spectroscopy ; Male ; Mannose Receptor ; Mice ; Microscopy, Atomic Force ; NIH 3T3 Cells ; Plasmids/metabolism ; Polyelectrolytes ; Scattering, Radiation ; Succinimides/chemistry |
| مستخلص: | 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. (© 2021 Wiley-VCH GmbH.) |
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| معلومات مُعتمدة: | R01 NS102412 United States NS NINDS NIH HHS; R01 NS112019 United States NS NINDS NIH HHS; R21 CA220148 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: cationic block copolymer; macrophage transfection; mannose; targeted gene delivery |
| المشرفين على المادة: | 0 (Cations) 0 (Cross-Linking Reagents) 0 (Ligands) 0 (Mannose Receptor) 0 (Polyelectrolytes) 0 (Polymers) 0 (Succinimides) 0 (polycations) 25104-18-1 (Polylysine) 3WJQ0SDW1A (Polyethylene Glycols) 9007-49-2 (DNA) EVY5D0U6SH (dithiobis(succinimidylpropionate)) PHA4727WTP (Mannose) Z0H242BBR1 (Aspartame) |
| تواريخ الأحداث: | Date Created: 20210222 Date Completed: 20211220 Latest Revision: 20231111 |
| رمز التحديث: | 20231111 |
| مُعرف محوري في PubMed: | PMC8126558 |
| DOI: | 10.1002/mabi.202000371 |
| PMID: | 33615675 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1616-5195 |
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| DOI: | 10.1002/mabi.202000371 |