pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery
Received 7 October 2017
Accepted for publication 7 December 2017
Published 31 January 2018 Volume 2018:13 Pages 641—652
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Linlin Sun
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
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