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 pro-duction. 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-kappa B) 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.

Wojnilowicz, M., Laznickova, P., Ju, Y., Ang, C., Tidu, F., Bendickova, K., et al. (2022). Influence of protein corona on the interaction of glycogen-siRNA constructs with ex vivo human blood immune cells. BIOMATERIALS ADVANCES, 140 [10.1016/j.bioadv.2022.213083].

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

Forte, Giancarlo;Cavalieri, Francesca
;
2022

Abstract

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 pro-duction. 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-kappa B) 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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/02
English
Glycogen nanoparticles; Peripheral blood mononuclear cells; Phagocytosis; Protein corona; Stochastic optical reconstruction microscopy; THP-1; siRNA glycoplexes; Blood Proteins; Glycogen; Leukocytes, Mononuclear; RNA, Small Interfering
Wojnilowicz, M., Laznickova, P., Ju, Y., Ang, C., Tidu, F., Bendickova, K., et al. (2022). Influence of protein corona on the interaction of glycogen-siRNA constructs with ex vivo human blood immune cells. BIOMATERIALS ADVANCES, 140 [10.1016/j.bioadv.2022.213083].
Wojnilowicz, M; Laznickova, P; Ju, Y; Ang, C; Tidu, F; Bendickova, K; Forte, G; Plebanski, M; Caruso, F; Cavalieri, F; Fric, J
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/308194
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