Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery

TL;DR

This study evaluates the biocompatibility and immune response of functionalized mesoporous silica nanoparticles, demonstrating their potential as safe, non-toxic drug delivery vehicles that can be activated to provoke immune responses when loaded with specific drugs.

Contribution

It provides new insights into the immunotoxicity profile of functionalized MSN and shows their ability to deliver drugs without inducing significant immune activation unless specifically triggered.

Findings

MSN are rapidly taken up by immune cells

Cargo-free MSN show low toxicity and immune activation

Loaded MSN with TLR7 agonist provoke strong immune responses

Abstract

Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1\beta. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications.