pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery

Shini Feng,1 Huijie Zhang,2 Chunyi Zhi,3 Xiao-Dong Gao,1 Hideki Nakanishi1 1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People’s Republic of China; 2School of Pharmaceutical Sciences, Jiangnan Unive...

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Autores principales:	Feng SN, Zhang HJ, Zhi CY, Gao XD, Nakanishi H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Boron nitride nanospheres drug delivery doxorubicin pH-responsive charge-reversal controlled release Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7ef9a4fad61c48f3ab6fddaf154a7dbb
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spelling	oai:doaj.org-article:7ef9a4fad61c48f3ab6fddaf154a7dbb2021-12-02T07:47:01ZpH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery1178-2013https://doaj.org/article/7ef9a4fad61c48f3ab6fddaf154a7dbb2018-01-01T00:00:00Zhttps://www.dovepress.com/ph-responsive-charge-reversal-polymer-functionalized-boron-nitride-nan-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shini Feng,1 Huijie Zhang,2 Chunyi Zhi,3 Xiao-Dong Gao,1 Hideki Nakanishi1 1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People’s Republic of China; 2School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China; 3Department of Physics and Materials Science, City University of Hong Kong, Kowloon, Hong Kong SAR, People’s Republic of China Background: Anticancer drug-delivery systems (DDSs) capable of responding to the physiological stimuli and efficiently releasing drugs inside tumor cells are highly desirable for effective cancer therapy. Herein, pH-responsive, charge-reversal poly(allylamine hydrochlorid)-citraconic anhydride (PAH-cit) functionalized boron nitride nanospheres (BNNS) were fabricated and used as a carrier for the delivery and controlled release of doxorubicin (DOX) into cancer cells.Methods: BNNS was synthesized through a chemical vapor deposition method and then functionalized with synthesized charge-reversal PAH-cit polymer. DOX@PAH-cit–BNNS complexes were prepared via step-by-step electrostatic interactions and were fully characterized. The cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release inside cancer cells were visualized by confocal laser scanning microscopy. The in vitro anticancer activity of DOX@PAH-cit–BNNS was examined using CCK-8 and live/dead viability/cytotoxicity assay. Results: The PAH-cit–BNNS complexes were nontoxic to normal and cancer cells up to a concentration of 100 µg/mL. DOX was loaded on PAH-cit–BNNS complexes with high efficiency. In a neutral environment, the DOX@PAH-cit–BNNS was stable, whereas the loaded DOX was effectively released from these complexes at low pH condition due to amide hydrolysis of PAH-cit. Enhanced cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release in the nucleus of cancer cells were revealed by confocal microscopy. Additionally, the effective delivery and release of DOX into the nucleus of cancer cells led to high therapeutic efficiency.Conclusion: Our findings indicated that the newly developed PAH-cit–BNNS complexes are promising as an efficient pH-responsive DDS for cancer therapy. Keywords: boron nitride nanospheres, drug delivery, doxorubicin, pH-responsive charge-reversal, controlled releaseFeng SNZhang HJZhi CYGao XDNakanishi HDove Medical PressarticleBoron nitride nanospheresdrug deliverydoxorubicinpH-responsive charge-reversalcontrolled releaseMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 641-652 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Boron nitride nanospheres drug delivery doxorubicin pH-responsive charge-reversal controlled release Medicine (General) R5-920
spellingShingle	Boron nitride nanospheres drug delivery doxorubicin pH-responsive charge-reversal controlled release Medicine (General) R5-920 Feng SN Zhang HJ Zhi CY Gao XD Nakanishi H pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery
description	Shini Feng,1 Huijie Zhang,2 Chunyi Zhi,3 Xiao-Dong Gao,1 Hideki Nakanishi1 1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People’s Republic of China; 2School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China; 3Department of Physics and Materials Science, City University of Hong Kong, Kowloon, Hong Kong SAR, People’s Republic of China Background: Anticancer drug-delivery systems (DDSs) capable of responding to the physiological stimuli and efficiently releasing drugs inside tumor cells are highly desirable for effective cancer therapy. Herein, pH-responsive, charge-reversal poly(allylamine hydrochlorid)-citraconic anhydride (PAH-cit) functionalized boron nitride nanospheres (BNNS) were fabricated and used as a carrier for the delivery and controlled release of doxorubicin (DOX) into cancer cells.Methods: BNNS was synthesized through a chemical vapor deposition method and then functionalized with synthesized charge-reversal PAH-cit polymer. DOX@PAH-cit–BNNS complexes were prepared via step-by-step electrostatic interactions and were fully characterized. The cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release inside cancer cells were visualized by confocal laser scanning microscopy. The in vitro anticancer activity of DOX@PAH-cit–BNNS was examined using CCK-8 and live/dead viability/cytotoxicity assay. Results: The PAH-cit–BNNS complexes were nontoxic to normal and cancer cells up to a concentration of 100 µg/mL. DOX was loaded on PAH-cit–BNNS complexes with high efficiency. In a neutral environment, the DOX@PAH-cit–BNNS was stable, whereas the loaded DOX was effectively released from these complexes at low pH condition due to amide hydrolysis of PAH-cit. Enhanced cellular uptake of DOX@PAH-cit–BNNS complexes and DOX release in the nucleus of cancer cells were revealed by confocal microscopy. Additionally, the effective delivery and release of DOX into the nucleus of cancer cells led to high therapeutic efficiency.Conclusion: Our findings indicated that the newly developed PAH-cit–BNNS complexes are promising as an efficient pH-responsive DDS for cancer therapy. Keywords: boron nitride nanospheres, drug delivery, doxorubicin, pH-responsive charge-reversal, controlled release
format	article
author	Feng SN Zhang HJ Zhi CY Gao XD Nakanishi H
author_facet	Feng SN Zhang HJ Zhi CY Gao XD Nakanishi H
author_sort	Feng SN
title	pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery
title_short	pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery
title_full	pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery
title_fullStr	pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery
title_full_unstemmed	pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery
title_sort	ph-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/7ef9a4fad61c48f3ab6fddaf154a7dbb
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pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery

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