Nanoparticle uptake screen

Understanding how cells process nanoparticles is crucial to optimize nanomedicine efficacy. However, characterizing cellular pathways is challenging, especially if non-canonical mechanisms are involved. Here, a genome-wide forward genetic screening based on insertional mutagenesis was applied to discover novel targets involved in the intracellular accumulation (uptake and intracellular processing) of silica nanoparticles. The nanoparticles were covered by a human serum corona known to target the low-density lipoprotein receptor (LDLR). By sorting cells with reduced nanoparticle amounts and deep sequencing after each sorting, 80 enriched genes were identified. We found that next to LDLR, the scavenger receptor SCARB1 mediates nanoparticle accumulation. Additionally, heparan sulphate act as specific nanoparticle receptor, and its role varies depending on cell and nanoparticle type. Furthermore, some of the identified targets affect nanoparticle trafficking to the lysosomes. These results show the potential of genetic screening to characterize nanoparticle pathways. Additionally, they indicate that corona-coated nanoparticles are internalized via multiple receptors.