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A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors

Strategies to target nanoparticles to tumors that rely on surface modification with ligands that bind molecules overexpressed on cancer cells or the tumor neovasculature suffer from a major limitation: with delivery of toxic agents the amount of molecules available for targeting decreases with time;...

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Autores principales: Chen, Zeming, Patel, Jaymin M., Noble, Philip W., Garcia, Cesar, Hong, Zhangyong, Hansen, James E., Zhou, Jiangbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312362/
https://www.ncbi.nlm.nih.gov/pubmed/27494868
http://dx.doi.org/10.18632/oncotarget.11015
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author Chen, Zeming
Patel, Jaymin M.
Noble, Philip W.
Garcia, Cesar
Hong, Zhangyong
Hansen, James E.
Zhou, Jiangbing
author_facet Chen, Zeming
Patel, Jaymin M.
Noble, Philip W.
Garcia, Cesar
Hong, Zhangyong
Hansen, James E.
Zhou, Jiangbing
author_sort Chen, Zeming
collection PubMed
description Strategies to target nanoparticles to tumors that rely on surface modification with ligands that bind molecules overexpressed on cancer cells or the tumor neovasculature suffer from a major limitation: with delivery of toxic agents the amount of molecules available for targeting decreases with time; consequently, the efficiency of nanoparticle delivery is reduced. To overcome this limitation, here we propose an autocatalytic tumor-targeting mechanism based on targeting extracellular DNA (exDNA). exDNA is enriched in the tumor microenviroment and increases with treatment with cytotoxic agents, such as doxorubicin (DOX), due to release of DNA by dying tumor cells. We tested this approach using poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface-conjugated with fragments of 3E10 (3E10(EN)), a lupus anti-DNA autoantibody. We demonstrated that 3E10(EN)-conjugated nanoparticles bound to DNA and preferentially localized to tumors in vivo. The efficiency of tumor localization of 3E10(EN)-conjugated, DOX-loaded nanoparticles increased with time and subsequent treatments, demonstrating an autocatalytic effect. 3E10(EN)-conjugated DOX-loaded nanoparticles exhibited a significant anti-tumor effect that was superior to all controls. This work demonstrates the promise of autocatalytic drug delivery mechanisms and establishes proof of concept for a new anti-DNA autoantibody-based approach for enhancing delivery of nanoparticles to tumors.
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spelling pubmed-53123622017-03-06 A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors Chen, Zeming Patel, Jaymin M. Noble, Philip W. Garcia, Cesar Hong, Zhangyong Hansen, James E. Zhou, Jiangbing Oncotarget Research Paper Strategies to target nanoparticles to tumors that rely on surface modification with ligands that bind molecules overexpressed on cancer cells or the tumor neovasculature suffer from a major limitation: with delivery of toxic agents the amount of molecules available for targeting decreases with time; consequently, the efficiency of nanoparticle delivery is reduced. To overcome this limitation, here we propose an autocatalytic tumor-targeting mechanism based on targeting extracellular DNA (exDNA). exDNA is enriched in the tumor microenviroment and increases with treatment with cytotoxic agents, such as doxorubicin (DOX), due to release of DNA by dying tumor cells. We tested this approach using poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface-conjugated with fragments of 3E10 (3E10(EN)), a lupus anti-DNA autoantibody. We demonstrated that 3E10(EN)-conjugated nanoparticles bound to DNA and preferentially localized to tumors in vivo. The efficiency of tumor localization of 3E10(EN)-conjugated, DOX-loaded nanoparticles increased with time and subsequent treatments, demonstrating an autocatalytic effect. 3E10(EN)-conjugated DOX-loaded nanoparticles exhibited a significant anti-tumor effect that was superior to all controls. This work demonstrates the promise of autocatalytic drug delivery mechanisms and establishes proof of concept for a new anti-DNA autoantibody-based approach for enhancing delivery of nanoparticles to tumors. Impact Journals LLC 2016-08-02 /pmc/articles/PMC5312362/ /pubmed/27494868 http://dx.doi.org/10.18632/oncotarget.11015 Text en Copyright: © 2016 Chen et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Zeming
Patel, Jaymin M.
Noble, Philip W.
Garcia, Cesar
Hong, Zhangyong
Hansen, James E.
Zhou, Jiangbing
A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
title A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
title_full A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
title_fullStr A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
title_full_unstemmed A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
title_short A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
title_sort lupus anti-dna autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312362/
https://www.ncbi.nlm.nih.gov/pubmed/27494868
http://dx.doi.org/10.18632/oncotarget.11015
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