Immune Modulation with Nanodiscs: Surface Charge Dictates Cellular Interactions and Activation of Macrophages and Dendritic-like Cells

TL;DR

This study shows how the surface charge of nanodiscs affects immune cell responses, with anionic nanodiscs causing more immune activation than neutral ones.

Contribution

The study introduces a human in vitro model to evaluate how nanodisc surface charge modulates macrophage and dendritic cell responses.

Findings

Anionic glyco-DIBMA nanodiscs increased immune cell activation and cytokine release.

Electroneutral sulfo-DIBMA nanodiscs showed minimal immune activation and reduced uptake.

Glyco-DIBMA nanodiscs promoted dendritic cell maturation and T-cell activation potential.

Abstract

The immunological barrier is among the most significant barriers in vivo. Macrophages and dendritic cells play a crucial role in immune responses, involving phagocytosis, antigen presentation, and triggering adaptive responses. Nanoscale drug-delivery vehicles, such as polymer-encapsulated lipid-bilayer nanodiscs, are of particular interest in the development of new therapeutic approaches, but require well-characterized human in vitro cell models. To this end, the present study differentiated human monocytes into two distinct states, resting macrophages and immature dendritic-like cells (iDCs). These cells served as model systems to assess the efficacy of lipid-bilayer nanodiscs encapsulated by anionic glyco-DIBMA (diisobutylene–maleic acid) or electroneutral sulfo-DIBMA polymers. Nanodisc–cell interaction studies—including cell viability, reactive oxygen species production, cytokine release, particle uptake, and activation marker expression—demonstrated that immune responses depend sensitively on the cell type and polymer and thus on the surface charge of the nanodiscs. Sulfo-DIBMA nanodiscs induced minimal immune cell activation, accompanied by cytokine release and reduced uptake of the nanodiscs by immune cells. In contrast, glyco-DIBMA nanodiscs exhibited increased interactions with cells, elicited pro-inflammatory immune responses, and promoted iDC maturation. This involved co-stimulatory and antigen-presenting molecules, potentially leading to T-cell activation. These findings underscore the potential of glyco-DIBMA nanodiscs to modulate immune responses through receptor-specific interactions, paving the way for immunotherapeutic strategies.

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