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Lookup NU author(s): Professor Moein MoghimiORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 The Authors. Advanced Functional Materials published by Wiley-VCH GmbHThe authors aim to develop siRNA therapeutics for cancer that can be administered systemically to target tumors and retard their growth. The efficacy of systemic delivery of siRNA to tumors with nanoparticles based on lipids or polymers is often compromised by their rapid clearance from the circulation by the liver. Here, multifunctional cationic and anionic siRNA nanoparticle formulations are described, termed receptor-targeted nanocomplexes (RTNs), that comprise peptides for siRNA packaging into nanoparticles and receptor-mediated cell uptake, together with lipids that confer nanoparticles with stealth properties to enhance stability in the circulation, and fusogenic properties to enhance endosomal release within the cell. Intravenous administration of RTNs in mice leads to predominant accumulation in xenograft tumors, with very little detected in the liver, lung, or spleen. Although non-targeted RTNs also enter the tumor, cell uptake appears to be RGD peptide-dependent indicating integrin-mediated uptake. RTNs with siRNA against MYCN (a member of the Myc family of transcription factors) in mice with MYCN-amplified neuroblastoma tumors show significant retardation of xenograft tumor growth and enhanced survival. This study shows that RTN formulations can achieve specific tumor-targeting, with minimal clearance by the liver and so enable delivery of tumor-targeted siRNA therapeutics.
Author(s): Tagalakis AD, Jayarajan V, Maeshima R, Ho KH, Syed F, Wu L-P, Aldossary AM, Munye MM, Mistry T, Ogunbiyi OK, Sala A, Standing JF, Moghimi SM, Stoker AW, Hart SL
Publication type: Article
Publication status: Published
Journal: Advanced Functional Materials
Year: 2021
Volume: 31
Issue: 37
Print publication date: 09/09/2021
Online publication date: 30/06/2021
Acceptance date: 02/04/2018
Date deposited: 21/07/2023
ISSN (print): 1616-301X
ISSN (electronic): 1616-3028
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/adfm.202104843
DOI: 10.1002/adfm.202104843
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