J 2022

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

WOJNILOWICZ, Marcin; Petra LÁZNIČKOVÁ; Yi JU; Ching-Seng ANG; Federico TIDU et al.

Základní údaje

Originální název

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

Autoři

WOJNILOWICZ, Marcin; Petra LÁZNIČKOVÁ ORCID; Yi JU; Ching-Seng ANG; Federico TIDU; Kamila BENDICKOVA; Giancarlo FORTE; Magdalena PLEBANSKI; Frank CARUSO; Francesca CAVALIERI a Jan FRIČ

Vydání

BIOMATERIALS ADVANCES, AMSTERDAM, ELSEVIER, 2022, 2772-9508

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30404 Biomaterials

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/22:00128439

Organizační jednotka

Lékařská fakulta

EID Scopus

Klíčová slova anglicky

Glycogen nanoparticles; siRNA glycoplexes; Peripheral blood mononuclear cells; THP-1; Phagocytosis; Protein corona; Stochastic optical reconstruction microscopy

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 31. 1. 2023 12:40, Mgr. Tereza Miškechová

Anotace

V originále

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.