Intracellular Delivery and Triggered Release of DNA Using Biodegradable Poly(2‐hydroxypropylene imine)s Containing Cystamine Units

Bočkuvienė, Alma; Slavuckyte, Kristina; Vareikis, Aušvydas; Zigmantas, Sarunas; Zaliauskiene, Lolita; Makuška, Ričardas

doi:10.1002/mabi.201600155

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…[ 41 ] The cellular toxicity of poly(2‐hydroxypropilene imine) (PHPI)‐based polyplexes was also reduced with the introduction of disulfide linkages. [ 42 ]…”

Section: Introductionmentioning

confidence: 99%

Mannosylated Cationic Copolymers for Gene Delivery to Macrophages

Lopukhov

Yang

Haney

et al. 2021

Macromolecular Bioscience

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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.

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“…[ 41 ] The cellular toxicity of poly(2‐hydroxypropilene imine) (PHPI)‐based polyplexes was also reduced with the introduction of disulfide linkages. [ 42 ]…”

Section: Introductionmentioning

confidence: 99%