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.

Basic information

Original name

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

Authors

WOJNILOWICZ, Marcin, Petra LÁZNIČKOVÁ (203 Czech Republic, belonging to the institution), Yi JU, Ching-Seng ANG, Federico TIDU (380 Italy), Kamila BENDICKOVA, Giancarlo FORTE (380 Italy), Magdalena PLEBANSKI, Frank CARUSO, Francesca CAVALIERI and Jan FRIČ (203 Czech Republic, guarantor)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30404 Biomaterials

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

RIV identification code

RIV/00216224:14110/22:00128439

Organization unit

Faculty of Medicine

UT WoS

000861397600003

Keywords in English

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

Tags

Tags

International impact, Reviewed
Změněno: 31/1/2023 12:40, Mgr. Tereza Miškechová

Abstract

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.