학술논문
High-throughput screens identify a lipid nanoparticle that preferentially delivers mRNA to human tumors in vivo.
Document Type
Academic Journal
Author
Huayamares SG; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Lokugamage MP; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Rab R; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.; Da Silva Sanchez AJ; 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.; Kim H; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Radmand A; 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.; Loughrey D; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Lian L; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Hou Y; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.; Achyut BR; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.; Ehrhardt A; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.; Hong JS; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA.; Sago CD; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Paunovska K; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Echeverri ES; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Vanover D; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Santangelo PJ; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.; Sorscher EJ; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA. Electronic address: esorscher@emory.edu.; Dahlman JE; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: james.dahlman@bme.gatech.edu.
Source
Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
Subject
Language
English
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.
Competing Interests: Declaration of Competing Interest J.E.D. is an advisor to GV. E.J.S. has ownership interest in PNP Therapeutics, Inc. and serves on the Board of Directors for the company, which develops products used in cancer research. Dr. Sorscher is also an inventor of technology being evaluated in studies described by this report. The terms of this arrangement for Dr. Sorscher have been reviewed and approved by Emory University in accordance with its conflict-of-interest policies. Dr. Jeong Hong also has minor equity interest in this company. All other authors declare no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of Competing Interest J.E.D. is an advisor to GV. E.J.S. has ownership interest in PNP Therapeutics, Inc. and serves on the Board of Directors for the company, which develops products used in cancer research. Dr. Sorscher is also an inventor of technology being evaluated in studies described by this report. The terms of this arrangement for Dr. Sorscher have been reviewed and approved by Emory University in accordance with its conflict-of-interest policies. Dr. Jeong Hong also has minor equity interest in this company. All other authors declare no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)