Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer

Parichart Naruphontjirakul,1 Kwanchanok Viravaidya-Pasuwat1,21Biological Engineering Program, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, Bangkok, Thailand; 2Department of Chemical Engineering, Faculty of Engineering, King Mongkut’s University of Tec...

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Autores principales: Naruphontjirakul P, Viravaidya-Pasuwat K
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:e14f08e3fa7345429becd538c80dd2b72021-12-02T08:04:43ZDevelopment of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer1178-2013https://doaj.org/article/e14f08e3fa7345429becd538c80dd2b72019-06-01T00:00:00Zhttps://www.dovepress.com/development-of-anti-her2-targeted-doxorubicin-core-shell-chitosan-nano-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Parichart Naruphontjirakul,1 Kwanchanok Viravaidya-Pasuwat1,21Biological Engineering Program, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, Bangkok, Thailand; 2Department of Chemical Engineering, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, Bangkok, ThailandPurpose: Doxorubicin (DOX) encapsulated O-succinyl chitosan graft Pluronic® F127 (OCP) copolymer nanoparticles conjugated with an anti-HER2 monoclonal antibody were developed as targeted drug delivery vehicles for the treatment of HER2-overexpressing breast cancer.Methods: Five percent and 10% (w/w) of O-succinyl chitosan was grafted onto Pluronic® F127 using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) as mediated cross-linking agents. DOX was added to the copolymer solution to form DOX-nanoparticles before conjugation with anti-HER2 on the surface of the nanoparticles.Results: DOX was encapsulated within the NP matrices at an encapsulation efficiency of 73.69 ± 0.53% to 74.65 ± 0.44% (the initial DOX concentration was 5 μg/mL). Anti-HER2 was successfully conjugated onto the surface of the nanoparticles at a moderately high conjugation efficiency of approximately 57.23 ± 0.38% to 61.20 ± 4.42%. In the in vitro DOX dissolution study, the nanoparticle formulations exhibited a biphasic drug release with an initial burst release followed by a sustained release profile at both pH 5.0 and pH 7.4. The drug was rapidly and completely released from the nanoparticles at pH 5.0. In the in vitro cytotoxicity, the anti-HER2 conjugated OCP copolymer nanoparticles showed the lowest IC50, which indicated an increase in the therapeutic efficacy of DOX to treat human breast cancer cells with the HER2 overexpression.Conclusion: Our study shows that anti-HER2 conjugated OCP copolymer nanoparticles have the potential for the development of anticancer drug carriers.Keywords: pluronic grafted chitosan, core-shell nanoparticles, doxorubicin, anti-HER2, MCF-7Naruphontjirakul PViravaidya-Pasuwat KDove Medical PressarticlePluronic grafted chitosancore-shell nanoparticlesdoxorubicinanti-HER2MCF-7Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 4105-4121 (2019)
institution DOAJ
collection DOAJ
language EN
topic Pluronic grafted chitosan
core-shell nanoparticles
doxorubicin
anti-HER2
MCF-7
Medicine (General)
R5-920
spellingShingle Pluronic grafted chitosan
core-shell nanoparticles
doxorubicin
anti-HER2
MCF-7
Medicine (General)
R5-920
Naruphontjirakul P
Viravaidya-Pasuwat K
Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer
description Parichart Naruphontjirakul,1 Kwanchanok Viravaidya-Pasuwat1,21Biological Engineering Program, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, Bangkok, Thailand; 2Department of Chemical Engineering, Faculty of Engineering, King Mongkut’s University of Technology Thonburi, Bangkok, ThailandPurpose: Doxorubicin (DOX) encapsulated O-succinyl chitosan graft Pluronic® F127 (OCP) copolymer nanoparticles conjugated with an anti-HER2 monoclonal antibody were developed as targeted drug delivery vehicles for the treatment of HER2-overexpressing breast cancer.Methods: Five percent and 10% (w/w) of O-succinyl chitosan was grafted onto Pluronic® F127 using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) as mediated cross-linking agents. DOX was added to the copolymer solution to form DOX-nanoparticles before conjugation with anti-HER2 on the surface of the nanoparticles.Results: DOX was encapsulated within the NP matrices at an encapsulation efficiency of 73.69 ± 0.53% to 74.65 ± 0.44% (the initial DOX concentration was 5 μg/mL). Anti-HER2 was successfully conjugated onto the surface of the nanoparticles at a moderately high conjugation efficiency of approximately 57.23 ± 0.38% to 61.20 ± 4.42%. In the in vitro DOX dissolution study, the nanoparticle formulations exhibited a biphasic drug release with an initial burst release followed by a sustained release profile at both pH 5.0 and pH 7.4. The drug was rapidly and completely released from the nanoparticles at pH 5.0. In the in vitro cytotoxicity, the anti-HER2 conjugated OCP copolymer nanoparticles showed the lowest IC50, which indicated an increase in the therapeutic efficacy of DOX to treat human breast cancer cells with the HER2 overexpression.Conclusion: Our study shows that anti-HER2 conjugated OCP copolymer nanoparticles have the potential for the development of anticancer drug carriers.Keywords: pluronic grafted chitosan, core-shell nanoparticles, doxorubicin, anti-HER2, MCF-7
format article
author Naruphontjirakul P
Viravaidya-Pasuwat K
author_facet Naruphontjirakul P
Viravaidya-Pasuwat K
author_sort Naruphontjirakul P
title Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer
title_short Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer
title_full Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer
title_fullStr Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer
title_full_unstemmed Development of anti-HER2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer
title_sort development of anti-her2-targeted doxorubicin–core-shell chitosan nanoparticles for the treatment of human breast cancer
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/e14f08e3fa7345429becd538c80dd2b7
work_keys_str_mv AT naruphontjirakulp developmentofantiher2targeteddoxorubicinndashcoreshellchitosannanoparticlesforthetreatmentofhumanbreastcancer
AT viravaidyapasuwatk developmentofantiher2targeteddoxorubicinndashcoreshellchitosannanoparticlesforthetreatmentofhumanbreastcancer
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