High-throughput screens identify a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo

Lipid nanoparticles (LNPs) are a clinically relevant way to deliver therapeutic mRNA to hepatocytes in patients. However, LNP-mRNA delivery to end-stage solid tumors such as head and neck squamous cell carcinoma (HNSCC) remains more challenging. While scientists have used in vitro assays to evaluate potential nanoparticles for HNSCC delivery, high-throughput delivery assays performed directly in vivo have not been reported. Here we use a high-throughput LNP assay to evaluate how 94 chemically distinct nanoparticles delivered nucleic acids to HNSCC solid tumors in vivo. DNA barcodes were used to identify LNP^HNSCC, a novel LNP for systemic delivery to HNSCC solid tumors. Importantly, LNP^HNSCC retains tropism to HNSCC solid tumors while minimizing off-target delivery to the liver.