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Influence of protein corona on the interaction of glycogen-siRNA constructs with ex vivo human blood immune cells

M. Wojnilowicz, P. Laznickova, Y. Ju, CS. Ang, F. Tidu, K. Bendickova, G. Forte, M. Plebanski, F. Caruso, F. Cavalieri, J. Fric

. 2022 ; 140 (-) : 213083. [pub] 20220818

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024514

Glycogen-nucleic acid constructs i.e., glycoplexes are emerging promising platforms for the alteration of gene expression and transcription. Understanding the interaction of glycoplexes with human blood components, such as serum proteins and peripheral blood mononuclear cells (PBMCs), is important to overcome immune cell activation and control biodistribution upon administration of the glycoplexes in vivo. Herein, we investigated the interactions of polyethylene glycol (PEG)ylated and non-PEGylated glycoplexes carrying siRNA molecules with PBMCs isolated from the blood of healthy donors. We found that both types of glycoplexes were non-toxic and were primarily phagocytosed by monocytes without triggering a pro-inflammatory interleukin 6 cytokine production. Furthermore, we investigated the role of the protein corona on controlling the internalization efficiency in immune cells - we found that the adsorption of serum proteins, in particular haptoglobin, alpha-1-antitrypsin and apolipoprotein A-II, onto the non-PEGylated glycoplexes, significantly reduced the uptake of the glycoplexes by PBMCs. Moreover, the non-PEGylated glycoplexes were efficient in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) knockdown in monocytic THP-1 cell line. This study provides an insight into the rational design of glycogen-based nanocarriers for the safe delivery of siRNA without eliciting unwanted immune cell activation and efficient siRNA activity upon its delivery.

Citace poskytuje Crossref.org

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$a Glycogen-nucleic acid constructs i.e., glycoplexes are emerging promising platforms for the alteration of gene expression and transcription. Understanding the interaction of glycoplexes with human blood components, such as serum proteins and peripheral blood mononuclear cells (PBMCs), is important to overcome immune cell activation and control biodistribution upon administration of the glycoplexes in vivo. Herein, we investigated the interactions of polyethylene glycol (PEG)ylated and non-PEGylated glycoplexes carrying siRNA molecules with PBMCs isolated from the blood of healthy donors. We found that both types of glycoplexes were non-toxic and were primarily phagocytosed by monocytes without triggering a pro-inflammatory interleukin 6 cytokine production. Furthermore, we investigated the role of the protein corona on controlling the internalization efficiency in immune cells - we found that the adsorption of serum proteins, in particular haptoglobin, alpha-1-antitrypsin and apolipoprotein A-II, onto the non-PEGylated glycoplexes, significantly reduced the uptake of the glycoplexes by PBMCs. Moreover, the non-PEGylated glycoplexes were efficient in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) knockdown in monocytic THP-1 cell line. This study provides an insight into the rational design of glycogen-based nanocarriers for the safe delivery of siRNA without eliciting unwanted immune cell activation and efficient siRNA activity upon its delivery.
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$a Laznickova, Petra $u Center for Translational Medicine, International Clinical Research Center (ICRC), St Anne's University Hospital Brno, Pekarska 53, 656 91 Brno, Czech Republic; Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno-Bohunice, Czech Republic
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$a Ju, Yi $u Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia; School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria 3083, Australia
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$a Tidu, Federico $u Center for Translational Medicine, International Clinical Research Center (ICRC), St Anne's University Hospital Brno, Pekarska 53, 656 91 Brno, Czech Republic; Division of Cancer Biology, The Institute of Cancer Research: London, 123 Old Brompton Road, London SW73RP, United Kingdom
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$a Bendickova, Kamila $u Center for Translational Medicine, International Clinical Research Center (ICRC), St Anne's University Hospital Brno, Pekarska 53, 656 91 Brno, Czech Republic
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