Portal de Periódicos da CAPES

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

2023; Elsevier BV; Volume: 357; Linguagem: Inglês

10.1016/j.jconrel.2023.04.005

1873-4995

Sebastian G. Huayamares, Melissa P. Lokugamage, Regina Rab, Alejandro J. Da Silva Sanchez, Hyejin Kim, Afsane Radmand, David Loughrey, Liming Lian, Yuning Hou, Bhagelu R. Achyut, Annette Ehrhardt, Jeong S. Hong, Cory D. Sago, Kalina Paunovska, Elisa Schrader Echeverri, Daryll Vanover, Philip J. Santangelo, Eric J. Sorscher, James E. Dahlman,

SARS-CoV-2 and COVID-19 Research

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 LNPHNSCC, a novel LNP for systemic delivery to HNSCC solid tumors. Importantly, LNPHNSCC retains tropism to HNSCC solid tumors while minimizing off-target delivery to the liver.