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

J Control Release. 2023-04;

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

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摘要

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, a novel LNP for systemic delivery to HNSCC solid tumors. Importantly, LNP retains tropism to HNSCC solid... More