Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles

[Image: see text] Plant-derived Type I toxins are candidate anticancer therapeutics requiring cytosolic delivery into tumor cells. We tested a concept for two-stage delivery, whereby tumor cells precoated with an antibody-targeted gelonin toxin were killed by exposure to endosome-disrupting polymer...

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Autores principales: Su, Xingfang, Yang, Nicole, Wittrup, K. Dane, Irvine, Darrell J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2013
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646422/
https://www.ncbi.nlm.nih.gov/pubmed/23444913
http://dx.doi.org/10.1021/bm3019906
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author Su, Xingfang
Yang, Nicole
Wittrup, K. Dane
Irvine, Darrell J.
author_facet Su, Xingfang
Yang, Nicole
Wittrup, K. Dane
Irvine, Darrell J.
author_sort Su, Xingfang
collection PubMed
description [Image: see text] Plant-derived Type I toxins are candidate anticancer therapeutics requiring cytosolic delivery into tumor cells. We tested a concept for two-stage delivery, whereby tumor cells precoated with an antibody-targeted gelonin toxin were killed by exposure to endosome-disrupting polymer nanoparticles. Co-internalization of particles and tumor cell-bound gelonin led to cytosolic delivery and >50-fold enhancement of toxin efficacy. This approach allows the extreme potency of gelonin to be focused on tumors with significantly reduced potential for off-target toxicity.
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spelling pubmed-36464222013-05-07 Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles Su, Xingfang Yang, Nicole Wittrup, K. Dane Irvine, Darrell J. Biomacromolecules [Image: see text] Plant-derived Type I toxins are candidate anticancer therapeutics requiring cytosolic delivery into tumor cells. We tested a concept for two-stage delivery, whereby tumor cells precoated with an antibody-targeted gelonin toxin were killed by exposure to endosome-disrupting polymer nanoparticles. Co-internalization of particles and tumor cell-bound gelonin led to cytosolic delivery and >50-fold enhancement of toxin efficacy. This approach allows the extreme potency of gelonin to be focused on tumors with significantly reduced potential for off-target toxicity. American Chemical Society 2013-02-27 2013-04-08 /pmc/articles/PMC3646422/ /pubmed/23444913 http://dx.doi.org/10.1021/bm3019906 Text en Copyright © 2013 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Su, Xingfang
Yang, Nicole
Wittrup, K. Dane
Irvine, Darrell J.
Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles
title Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles
title_full Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles
title_fullStr Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles
title_full_unstemmed Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles
title_short Synergistic Antitumor Activity from Two-Stage Delivery of Targeted Toxins and Endosome-Disrupting Nanoparticles
title_sort synergistic antitumor activity from two-stage delivery of targeted toxins and endosome-disrupting nanoparticles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646422/
https://www.ncbi.nlm.nih.gov/pubmed/23444913
http://dx.doi.org/10.1021/bm3019906
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AT wittrupkdane synergisticantitumoractivityfromtwostagedeliveryoftargetedtoxinsandendosomedisruptingnanoparticles
AT irvinedarrellj synergisticantitumoractivityfromtwostagedeliveryoftargetedtoxinsandendosomedisruptingnanoparticles

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