Journal
RSC ADVANCES
Volume 4, Issue 39, Pages 20208-20215Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4ra01812e
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Funding
- National Natural Science Foundation of China [81170773]
- PCSIRT [IRT 1257]
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Currently, the major challenge for cancer treatment is to develop simple and smart nanocarriers that can efficiently retain the encapsulated drug during blood circulation, recognize tumor cells and quickly release the drug under stimulation. In this paper, such a pH-sensitive core-shell composite nanoparticles is prepared based on a 3-aminophenylboronic acid modified mesoporous silica nanoparticles (MSN-APBA) core coated with a lactobionic acid grafted chitosan (CS-LA) shell via boronate ester bonds. The MSN core increases drug loading capacity and stability, and lactobionic acid offers abundant diols which can form pH sensitive boronate ester bonds with APBA on MSN. Meanwhile, the lactobionic acid-conjugated shell could also efficiently target the asialoglycoprotein receptor over expressing hepatoma cells. The successful synthesis of CS-LA and MSN-APBA is confirmed by the results of TGA, TEM, DLS, FT-IR, H-1-NMR and N-2 adsorption-desorption. Doxorubicin hydrochloride (DOX) is applied as a model drug and the behaviors of drug loading/ release are investigated. The drug loading behavior is pH-dependent, and its drug encapsulation efficiency is near 80% and loading capacity is 13.05%. The results of cumulative in vitro release indicate that at neutral pH, the pores of the MSN are effectively capped with a polymer shell and the drug release is strongly inhibited, almost zero release. While at acidic pH, the hydrolysis of the boroester bond takes place and thus results in a rapid release of the entrapped drug. The cytotoxicity assay indicates high cell biocompatibility of this material and it is suitable as a drug carrier. When loaded with DOX, it presents distinctly cytotoxic behavior to HepG2 cells, due to the sustained release of drug. These results imply that the core-shell nanoparticles are promising platforms to construct simple and effective pH-responsive controlled drug delivery systems for cancer therapy.
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