LAUSR

Description High-throughput tool uncovers links between cell signaling and nanomaterial uptake The promise of chemotherapeutic nanomedicine has tantalized clinicians and patients for decades. Nanoparticles (NPs) can directly target tumor cells, which would reduce the amount of chemotherapy administered and its systemic toxicity, increasing patient quality of life and extending utility of therapies with lifetime dosing limits. However, these hopes remain largely unrealized. Liposomal drug carriers, which make up nearly all clinically approved nanomedicines, have not extended overall patient survival compared with treatment with the drugs alone (1). These failures have been attributed to poor delivery to target cells (2) because NPs must first traverse a series of biological barriers (3). Although nanocarrier composition, surface chemistry, size, and shape have been optimized to promote cell entry, progress has been confounded by heterogeneity in cell uptake signaling (4). On page 384 of this issue, Boehnke et al. (5) uncover the reciprocal relationship between NP material properties and cell internalization using nanoPRISM, a high-throughput screening approach.