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Cationic diblock copolymers of polyethylene glycol (PEG) and poly\u2010L\u2010lysine (PLL) or poly{N\u2010[N\u2010(2\u2010aminoethyl)\u20102\u2010aminoethyl]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\u2010<jats:italic>b<\/jats:italic>\u2010PLL copolymers are known for its cytotoxicity, so PEG\u2010<jats:italic>b<\/jats:italic>\u2010PLL\u2010based polyplexes are cross\u2010linked using reducible reagent dithiobis(succinimidyl propionate) (DSP). The cross\u2010linked polyplexes display low toxicity to both mouse embryonic fibroblasts NIH\/3T3 cell line and mouse bone marrow\u2010derived macrophages (BMM\u03a6). In macrophages mannose\u2010decorated polyplexes demonstrate an \u22488 times higher transfection efficiency. The cross\u2010linking of the polyplexes decrease the toxicity, but the transfection enhancement is moderate. The PEG\u2010<jats:italic>b<\/jats:italic>\u2010pAsp(DET) copolymers display low toxicity with respect to the IC\u201021 murine macrophage cell line and are used for the production of non\u2010cross\u2010linked pDNA\u2010contained polyplexes. The obtained mannose modified polyplexes exhibit ca. 500\u2010times greater transfection activity in IC\u201021 macrophages compared to the mannose\u2010free polyplexes. This result greatly exceeds the targeting gene transfer effects previously described using mannose receptor targeted non\u2010viral gene delivery systems. These results suggest that Man\u2010PEG\u2010<jats:italic>b<\/jats:italic>\u2010pAsp(DET)\/pDNA polyplex is a potential vector for immune cells\u2010based gene therapy.<\/jats:p>","DOI":"10.1002\/mabi.202000371","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T09:45:53Z","timestamp":1613987153000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Mannosylated Cationic Copolymers for Gene Delivery to Macrophages"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3517-505X","authenticated-orcid":false,"given":"Anton V.","family":"Lopukhov","sequence":"first","affiliation":[{"name":"Laboratory for Chemical Design of Bionanomaterials Faculty of Chemistry M. V. 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