Quantitative phase imaging analysis of silica nanoparticle-induced macrophage recovery and functionality

Uptake of nanoparticles by macrophages has long been a significant concern for systemically delivered nanoparticle-based therapeutics. While the accumulation of nanoparticles in macrophages reduces the availability of therapeutics at the target site, it also raises toxicity concerns, including diminished macrophage viability and functionality. Conventional in vitro assays to study nanoparticle toxicity in macrophages rely on endpoint measurements and may not always provide insights into nanoparticle toxicity over time. Real-time quantitative phase imaging (QPI) can provide details on changes in cellular mass, specific growth, population distribution, and cell viability.

Herein, we used QPI, alongside a conventional in vitro biological assay, to assess macrophage recovery and phagocytic activity for silica nanoparticles (SNPs) with different sizes and porosities. QPI assay enabled dynamic measurement of nanoparticle toxicity, including real-time monitoring of cells, tracking cellular mass over time, and measuring the specific growth rate. When combined with fluorescence, it allowed the study of macrophage phagocytic activity via bioparticle uptake and its effects at the single-cell level.

The recovery study showed dose-dependent macrophage recovery upon SNP-treatment, and the phagocytic assay showed no decrease in phagocytosis at nontoxic SNP concentrations.

This study shows that the QPI assay can complement traditional biological assays to investigate nanoparticle-induced toxicity.