Bio21 - Research Publications
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ItemInfluence of protein corona on the interaction of glycogen-siRNA constructs with ex vivo human blood immune cells(ELSEVIER, 2022-09)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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ItemProtein precoating modulates biomolecular coronas and nanocapsule-immune cell interactions in human blood(ROYAL SOC CHEMISTRY, 2022-09-28)The biomolecular corona that forms on particles upon contact with blood plays a key role in the fate and utility of nanomedicines. Recent studies have shown that precoating nanoparticles with serum proteins can improve the biocompatibility and stealth properties of nanoparticles. However, it is not fully clear how precoating influences biomolecular corona formation and downstream biological responses. Herein, we systematically examine three precoating strategies by coating bovine serum albumin (single protein), fetal bovine serum (FBS, mixed proteins without immunoglobulins), or bovine serum (mixed proteins) on three nanoparticle systems, namely supramolecular template nanoparticles, metal-phenolic network (MPN)-coated template (core-shell) nanoparticles, and MPN nanocapsules (obtained after template removal). The effect of protein precoating on biomolecular corona compositions and particle-immune cell interactions in human blood was characterized. In the absence of a pre-coating, the MPN nanocapsules displayed lower leukocyte association, which correlated to the lower amount (by 2-3 fold) of adsorbed proteins and substantially fewer immunoglobulins (more than 100 times) in the biomolecular corona relative to the template and core-shell nanoparticles. Among the three coating strategies, FBS precoating demonstrated the most significant reduction in leukocyte association (up to 97% of all three nanoparticles). A correlation analysis highlights that immunoglobulins and apolipoproteins may regulate leukocyte recognition. This study demonstrates the impact of different precoating strategies on nanoparticle-immune cell association and the role of immunoglobulins in bio-nano interactions.