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Tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid DNA

As the tumor microenvironment (TME) develops, it is critical to take the alterations of pH value, reduction and various enzymes of the TME into consideration when constructing the desirable co-delivery systems. Herein, TME pH and enzyme dual-responsive core–shell nanoparticles were prepared for the...

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Autores principales: Wang, Tianqi, Yu, Xiaoyue, Han, Leiqiang, Liu, Tingxian, Liu, Yongjun, Zhang, Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503489/
https://www.ncbi.nlm.nih.gov/pubmed/28740384
http://dx.doi.org/10.2147/IJN.S134378
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author Wang, Tianqi
Yu, Xiaoyue
Han, Leiqiang
Liu, Tingxian
Liu, Yongjun
Zhang, Na
author_facet Wang, Tianqi
Yu, Xiaoyue
Han, Leiqiang
Liu, Tingxian
Liu, Yongjun
Zhang, Na
author_sort Wang, Tianqi
collection PubMed
description As the tumor microenvironment (TME) develops, it is critical to take the alterations of pH value, reduction and various enzymes of the TME into consideration when constructing the desirable co-delivery systems. Herein, TME pH and enzyme dual-responsive core–shell nanoparticles were prepared for the efficient co-delivery of chemotherapy drug and plasmid DNA (pDNA). A novel pH-responsive, positively charged drug loading material, doxorubicin (DOX)-4-hydrazinobenzoic acid (HBA)-polyethyleneimine (PEI) conjugate (DOX-HBA-PEI, DHP), was synthesized to fabricate positively charged polyion complex inner core DHP/DNA nanoparticles (DDN). Hyaluronic acid (HA) was an enzyme-responsive shell which could protect the core and enhance the co-delivery efficiency through CD44-mediated endocytosis. The HA-shielded pH and enzyme dual-responsive nanoparticles (HDDN) were spherical with narrow distribution. The particle size of HDDN was 148.3±3.88 nm and the zeta potential was changed to negative (−18.1±2.03 mV), which led to decreased cytotoxicity. The cumulative release of DOX from DHP at pH 5.0 (66.4%) was higher than that at pH 7.4 (30.1%), which indicated the pH sensitivity of DHP. The transfection efficiency of HDDN in 10% serum was equal to that in the absence of serum, while the transfection of DDN was significantly decreased in the presence of 10% serum. Furthermore, cellular uptake studies and co-localization assay showed that HDDN were internalized effectively through CD44-mediated endocytosis in the tumor cells. The efficient co-delivery of DOX and pEGFP was confirmed by fluorescent image taken by laser confocal microscope. It can be concluded that TME dual-responsive HA-shielded core–shell nanoparticles could be considered as a promising platform for the co-delivery of chemotherapy drug and pDNA.
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spelling pubmed-55034892017-07-24 Tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid DNA Wang, Tianqi Yu, Xiaoyue Han, Leiqiang Liu, Tingxian Liu, Yongjun Zhang, Na Int J Nanomedicine Original Research As the tumor microenvironment (TME) develops, it is critical to take the alterations of pH value, reduction and various enzymes of the TME into consideration when constructing the desirable co-delivery systems. Herein, TME pH and enzyme dual-responsive core–shell nanoparticles were prepared for the efficient co-delivery of chemotherapy drug and plasmid DNA (pDNA). A novel pH-responsive, positively charged drug loading material, doxorubicin (DOX)-4-hydrazinobenzoic acid (HBA)-polyethyleneimine (PEI) conjugate (DOX-HBA-PEI, DHP), was synthesized to fabricate positively charged polyion complex inner core DHP/DNA nanoparticles (DDN). Hyaluronic acid (HA) was an enzyme-responsive shell which could protect the core and enhance the co-delivery efficiency through CD44-mediated endocytosis. The HA-shielded pH and enzyme dual-responsive nanoparticles (HDDN) were spherical with narrow distribution. The particle size of HDDN was 148.3±3.88 nm and the zeta potential was changed to negative (−18.1±2.03 mV), which led to decreased cytotoxicity. The cumulative release of DOX from DHP at pH 5.0 (66.4%) was higher than that at pH 7.4 (30.1%), which indicated the pH sensitivity of DHP. The transfection efficiency of HDDN in 10% serum was equal to that in the absence of serum, while the transfection of DDN was significantly decreased in the presence of 10% serum. Furthermore, cellular uptake studies and co-localization assay showed that HDDN were internalized effectively through CD44-mediated endocytosis in the tumor cells. The efficient co-delivery of DOX and pEGFP was confirmed by fluorescent image taken by laser confocal microscope. It can be concluded that TME dual-responsive HA-shielded core–shell nanoparticles could be considered as a promising platform for the co-delivery of chemotherapy drug and pDNA. Dove Medical Press 2017-07-04 /pmc/articles/PMC5503489/ /pubmed/28740384 http://dx.doi.org/10.2147/IJN.S134378 Text en © 2017 Wang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Wang, Tianqi
Yu, Xiaoyue
Han, Leiqiang
Liu, Tingxian
Liu, Yongjun
Zhang, Na
Tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid DNA
title Tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid DNA
title_full Tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid DNA
title_fullStr Tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid DNA
title_full_unstemmed Tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid DNA
title_short Tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid DNA
title_sort tumor microenvironment dual-responsive core–shell nanoparticles with hyaluronic acid-shield for efficient co-delivery of doxorubicin and plasmid dna
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503489/
https://www.ncbi.nlm.nih.gov/pubmed/28740384
http://dx.doi.org/10.2147/IJN.S134378
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