This paper introduces a novel ‘nanoPRISM’ method that leverages the PRISM cell set to understand the structure-function relationship of nanoparticles. For this study, the PR500 was treated with a library of modular fluorescent nanoparticles to understand regulators of nanoparticle delivery. In particular, SLC46A3 (a lysosomal transporter) was identified as a negative regulator of lipid-based nanoparticle uptake.