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Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival

The 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 circulat...

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Autores principales: Tagalakis, Aristides D., Jayarajan, Vignesh, Maeshima, Ruhina, Ho, Kin H., Syed, Farhatullah, Wu, Lin‐Ping, Aldossary, Ahmad M., Munye, Mustafa M., Mistry, Talisa, Ogunbiyi, Olumide Kayode, Sala, Arturo, Standing, Joseph F., Moghimi, Seyed M., Stoker, Andrew W., Hart, Stephen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178728/
https://www.ncbi.nlm.nih.gov/pubmed/35712226
http://dx.doi.org/10.1002/adfm.202104843
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author Tagalakis, Aristides D.
Jayarajan, Vignesh
Maeshima, Ruhina
Ho, Kin H.
Syed, Farhatullah
Wu, Lin‐Ping
Aldossary, Ahmad M.
Munye, Mustafa M.
Mistry, Talisa
Ogunbiyi, Olumide Kayode
Sala, Arturo
Standing, Joseph F.
Moghimi, Seyed M.
Stoker, Andrew W.
Hart, Stephen L.
author_facet Tagalakis, Aristides D.
Jayarajan, Vignesh
Maeshima, Ruhina
Ho, Kin H.
Syed, Farhatullah
Wu, Lin‐Ping
Aldossary, Ahmad M.
Munye, Mustafa M.
Mistry, Talisa
Ogunbiyi, Olumide Kayode
Sala, Arturo
Standing, Joseph F.
Moghimi, Seyed M.
Stoker, Andrew W.
Hart, Stephen L.
author_sort Tagalakis, Aristides D.
collection PubMed
description The 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.
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spelling pubmed-91787282022-06-14 Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival Tagalakis, Aristides D. Jayarajan, Vignesh Maeshima, Ruhina Ho, Kin H. Syed, Farhatullah Wu, Lin‐Ping Aldossary, Ahmad M. Munye, Mustafa M. Mistry, Talisa Ogunbiyi, Olumide Kayode Sala, Arturo Standing, Joseph F. Moghimi, Seyed M. Stoker, Andrew W. Hart, Stephen L. Adv Funct Mater Research Articles The 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. John Wiley and Sons Inc. 2021-06-30 2021-09-09 /pmc/articles/PMC9178728/ /pubmed/35712226 http://dx.doi.org/10.1002/adfm.202104843 Text en © 2021 The Authors. Advanced Functional Materials published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Tagalakis, Aristides D.
Jayarajan, Vignesh
Maeshima, Ruhina
Ho, Kin H.
Syed, Farhatullah
Wu, Lin‐Ping
Aldossary, Ahmad M.
Munye, Mustafa M.
Mistry, Talisa
Ogunbiyi, Olumide Kayode
Sala, Arturo
Standing, Joseph F.
Moghimi, Seyed M.
Stoker, Andrew W.
Hart, Stephen L.
Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival
title Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival
title_full Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival
title_fullStr Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival
title_full_unstemmed Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival
title_short Integrin‐Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor‐Specific Delivery Achieve MYCN Silencing with Improved Survival
title_sort integrin‐targeted, short interfering rna nanocomplexes for neuroblastoma tumor‐specific delivery achieve mycn silencing with improved survival
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178728/
https://www.ncbi.nlm.nih.gov/pubmed/35712226
http://dx.doi.org/10.1002/adfm.202104843
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