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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-01-01
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| Series: | International Journal of Nanomedicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/ph-responsive-charge-reversal-polymer-functionalized-boron-nitride-nan-peer-reviewed-article-IJN |
| _version_ | 1818852889291915264 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-19T07:28:05Z |
| format | Article |
| id | doaj.art-7ef9a4fad61c48f3ab6fddaf154a7dbb |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-19T07:28:05Z |
| publishDate | 2018-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-7ef9a4fad61c48f3ab6fddaf154a7dbb2022-12-21T20:30:47ZengDove Medical PressInternational Journal of Nanomedicine1178-20132018-01-01Volume 1364165236600pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin deliveryFeng SNZhang HJZhi CYGao XDNakanishi HShini 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 releasehttps://www.dovepress.com/ph-responsive-charge-reversal-polymer-functionalized-boron-nitride-nan-peer-reviewed-article-IJNBoron nitride nanospheresdrug deliverydoxorubicinpH-responsive charge-reversalcontrolled release |
| spellingShingle | Feng SN Zhang HJ Zhi CY Gao XD Nakanishi H pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery International Journal of Nanomedicine Boron nitride nanospheres drug delivery doxorubicin pH-responsive charge-reversal controlled release |
| title | 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_short | 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 |
| topic | Boron nitride nanospheres drug delivery doxorubicin pH-responsive charge-reversal controlled release |
| url | https://www.dovepress.com/ph-responsive-charge-reversal-polymer-functionalized-boron-nitride-nan-peer-reviewed-article-IJN |
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