Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 13, Issue -, Pages 641-652Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S153476
Keywords
boron nitride nanospheres; drug delivery; doxorubicin; pH-responsive chargereversal; controlled release
Funding
- Natural Science Foundation of Jiangsu Province [BK 20170202]
- National Natural Science of China [21778023, 21576118]
- 111 Project [111-2-06]
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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 mu g/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.
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