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

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

doi:10.1016/j.jconrel.2023.04.005

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

J Control Release. 2023 May:357:394-403. doi: 10.1016/j.jconrel.2023.04.005. Epub 2023 Apr 12.

Authors

Sebastian G Huayamares¹, Melissa P Lokugamage¹, Regina Rab², Alejandro J Da Silva Sanchez³, Hyejin Kim¹, Afsane Radmand³, David Loughrey¹, Liming Lian¹, Yuning Hou², Bhagelu R Achyut⁴, Annette Ehrhardt⁴, Jeong S Hong⁴, Cory D Sago¹, Kalina Paunovska¹, Elisa Schrader Echeverri¹, Daryll Vanover¹, Philip J Santangelo¹, Eric J Sorscher⁵, James E Dahlman⁶

Affiliations

¹ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
² Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
³ Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA; Department of Chemical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
⁴ Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.
⁵ Department of Pediatrics, Emory University, Atlanta, GA 30322, USA; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. Electronic address: [email protected].
⁶ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: [email protected].

Abstract

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.

Keywords: DNA barcode; Lipid nanoparticles; cancer; mRNA delivery.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Head and Neck Neoplasms* / genetics
Humans
Lipids
Nanoparticles*
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Squamous Cell Carcinoma of Head and Neck

Substances

Lipid Nanoparticles
RNA, Messenger
Lipids
RNA, Small Interfering

Grants and funding

R01 DE026941/DE/NIDCR NIH HHS/United States