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Highly stable RGD/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release

BACKGROUND: Stability, enhanced drug-loading efficiency (DLE), and specific accumulation of therapeutics at tumor sites remain major challenges for successful cancer therapy. PURPOSE: This study describes a newly developed intelligent nanosystem that integrates stealthy, active targeting, stimulus-r...

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Autores principales: Yan, Jianqin, Zhang, Hai, Cheng, Furong, He, Yanmei, Su, Ting, Zhang, Xuequan, Zhang, Man, Zhu, Yutong, Li, Congrui, Cao, Jun, He, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289232/
https://www.ncbi.nlm.nih.gov/pubmed/30584298
http://dx.doi.org/10.2147/IJN.S179906
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author Yan, Jianqin
Zhang, Hai
Cheng, Furong
He, Yanmei
Su, Ting
Zhang, Xuequan
Zhang, Man
Zhu, Yutong
Li, Congrui
Cao, Jun
He, Bin
author_facet Yan, Jianqin
Zhang, Hai
Cheng, Furong
He, Yanmei
Su, Ting
Zhang, Xuequan
Zhang, Man
Zhu, Yutong
Li, Congrui
Cao, Jun
He, Bin
author_sort Yan, Jianqin
collection PubMed
description BACKGROUND: Stability, enhanced drug-loading efficiency (DLE), and specific accumulation of therapeutics at tumor sites remain major challenges for successful cancer therapy. PURPOSE: This study describes a newly developed intelligent nanosystem that integrates stealthy, active targeting, stimulus-responsiveness, and π–π interaction properties in a single carrier, based on the multifunctional star-shaped biodegradable polyester. PATIENTS AND METHODS: This highly stable, smart nanocarrier with spherical structures and a low critical micelle concentration (CMC) can provide spacious harbor and strong π–π interaction and hydrophobic interactions for hydrophobic doxorubicin (DOX). Its structure and morphology were characterized by proton nuclear magnetic resonance (1H-NMR) spectra, Fourier transform infrared (FTIR) spectra, Gel permeation chromatography (GPC), dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Antitumor effciency of polymeric micelles using CCK-8 assay, and the intracellular-activated delivery system was tracked by confocal laser scanning microscopy (CLSM) and flow cytometry. RESULTS: The synthesized copolymer can be self-assembled into nanoparticles with size of 50 nm and critical micellar concentration of 2.10 µg/mL. The drug-loading content of nanoparticles can be enhanced to 17.35%. Additionally, the stimulus-responsive evaluation and drug release study showed that the nanocarrier can rapidly respond to the intracellular reductive environment and dissociate for drug release. An in vitro study demonstrated that the nanocarrier can ferry doxorubicin selectively into tumor tissue, rapidly enter cancer cells, and controllably release its payload in response to an intracellular reductive environment, resulting in excellent antitumor activity in vitro. CONCLUSION: This study provides a facile and versatile approach for the design of multifunctional star-shaped biodegradable polyester nanovehicles for effective cancer treatment.
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spelling pubmed-62892322018-12-24 Highly stable RGD/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release Yan, Jianqin Zhang, Hai Cheng, Furong He, Yanmei Su, Ting Zhang, Xuequan Zhang, Man Zhu, Yutong Li, Congrui Cao, Jun He, Bin Int J Nanomedicine Original Research BACKGROUND: Stability, enhanced drug-loading efficiency (DLE), and specific accumulation of therapeutics at tumor sites remain major challenges for successful cancer therapy. PURPOSE: This study describes a newly developed intelligent nanosystem that integrates stealthy, active targeting, stimulus-responsiveness, and π–π interaction properties in a single carrier, based on the multifunctional star-shaped biodegradable polyester. PATIENTS AND METHODS: This highly stable, smart nanocarrier with spherical structures and a low critical micelle concentration (CMC) can provide spacious harbor and strong π–π interaction and hydrophobic interactions for hydrophobic doxorubicin (DOX). Its structure and morphology were characterized by proton nuclear magnetic resonance (1H-NMR) spectra, Fourier transform infrared (FTIR) spectra, Gel permeation chromatography (GPC), dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Antitumor effciency of polymeric micelles using CCK-8 assay, and the intracellular-activated delivery system was tracked by confocal laser scanning microscopy (CLSM) and flow cytometry. RESULTS: The synthesized copolymer can be self-assembled into nanoparticles with size of 50 nm and critical micellar concentration of 2.10 µg/mL. The drug-loading content of nanoparticles can be enhanced to 17.35%. Additionally, the stimulus-responsive evaluation and drug release study showed that the nanocarrier can rapidly respond to the intracellular reductive environment and dissociate for drug release. An in vitro study demonstrated that the nanocarrier can ferry doxorubicin selectively into tumor tissue, rapidly enter cancer cells, and controllably release its payload in response to an intracellular reductive environment, resulting in excellent antitumor activity in vitro. CONCLUSION: This study provides a facile and versatile approach for the design of multifunctional star-shaped biodegradable polyester nanovehicles for effective cancer treatment. Dove Medical Press 2018-12-04 /pmc/articles/PMC6289232/ /pubmed/30584298 http://dx.doi.org/10.2147/IJN.S179906 Text en © 2018 Yan 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
Yan, Jianqin
Zhang, Hai
Cheng, Furong
He, Yanmei
Su, Ting
Zhang, Xuequan
Zhang, Man
Zhu, Yutong
Li, Congrui
Cao, Jun
He, Bin
Highly stable RGD/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release
title Highly stable RGD/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release
title_full Highly stable RGD/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release
title_fullStr Highly stable RGD/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release
title_full_unstemmed Highly stable RGD/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release
title_short Highly stable RGD/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release
title_sort highly stable rgd/disulfide bridge-bearing star-shaped biodegradable nanocarriers for enhancing drug-loading efficiency, rapid cellular uptake, and on-demand cargo release
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289232/
https://www.ncbi.nlm.nih.gov/pubmed/30584298
http://dx.doi.org/10.2147/IJN.S179906
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