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Lopukhov AV, Yang Z, Haney MJ, et al. Mannosylated Cationic Copolymers for Gene Delivery to Macrophages. Macromol Biosci. 2021;21(4):e2000371doi: 10.1002/mabi.202000371.
Lopukhov, A. V., Yang, Z., Haney, M. J., Bronich, T. K., Sokolsky-Papkov, M., Batrakova, E. V., Klyachko, N. L., & Kabanov, A. V. (2021). Mannosylated Cationic Copolymers for Gene Delivery to Macrophages. Macromolecular bioscience, 21(4), e2000371. https://doi.org/10.1002/mabi.202000371
Lopukhov, Anton V, et al. "Mannosylated Cationic Copolymers for Gene Delivery to Macrophages." Macromolecular bioscience vol. 21,4 (2021): e2000371. doi: https://doi.org/10.1002/mabi.202000371
Lopukhov AV, Yang Z, Haney MJ, Bronich TK, Sokolsky-Papkov M, Batrakova EV, Klyachko NL, Kabanov AV. Mannosylated Cationic Copolymers for Gene Delivery to Macrophages. Macromol Biosci. 2021 Apr;21(4):e2000371. doi: 10.1002/mabi.202000371. Epub 2021 Feb 22. PMID: 33615675; PMCID: PMC8126558.
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Macromol Biosci. 2021 Apr;21(4):e2000371. doi: 10.1002/mabi.202000371. Epub 2021 Feb 22.

Mannosylated Cationic Copolymers for Gene Delivery to Macrophages.

Macromolecular bioscience

Anton V Lopukhov, Zigang Yang, Matthew J Haney, Tatiana K Bronich, Marina Sokolsky-Papkov, Elena V Batrakova, Natalia L Klyachko, Alexander V Kabanov

Affiliations

  1. Laboratory for Chemical Design of Bionanomaterials, Faculty of Chemistry, M. V. Lomonosov Moscow State University, 1 Leninskie Gory, Moscow, 117234, Russia.
  2. 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.
  3. 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.

PMID: 33615675 PMCID: PMC8126558 DOI: 10.1002/mabi.202000371

Abstract

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.

Keywords: cationic block copolymer; macrophage transfection; mannose; targeted gene delivery

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