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Preparation of biocompatible heat-labile enterotoxin subunit B-bovine serum albumin nanoparticles for improving tumor-targeted drug delivery via heat-labile enterotoxin subunit B mediation

Authors Zhao L, Su R, Cui W, Shi Y, Liu L, Su C

Received 15 January 2014

Accepted for publication 10 March 2014

Published 6 May 2014 Volume 2014:9(1) Pages 2149—2156

DOI https://doi.org/10.2147/IJN.S60764

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Liang Zhao,1,* Rongjian Su,2,* Wenyu Cui,3 Yijie Shi,1 Liwei Liu,1 Chang Su4

1School of Pharmacy, Liaoning Medical University, Jinzhou, People's Republic of China; 2Central Laboratory of Liaoning Medical University, Jinzhou, People’s Republic of China; 3National Vaccine and Serum Institute, Beijing, People’s Republic of China; 4School of Veterinary Medicine, Liaoning Medical University, Jinzhou, People’s Republic of China

*These authors contributed equally to this work

Abstract: Heat-labile enterotoxin subunit B (LTB) is a non-catalytic protein from a pentameric subunit of Escherichia coli. Based on its function of binding specifically to ganglioside GM1 on the surface of cells, a novel nanoparticle (NP) composed of a mixture of bovine serum albumin (BSA) and LTB was designed for targeted delivery of 5-fluorouracil to tumor cells. BSA-LTB NPs were characterized by determination of their particle size, polydispersity, morphology, drug encapsulation efficiency, and drug release behavior in vitro. The internalization of fluorescein isothiocyanate-labeled BSA-LTB NPs into cells was observed using fluorescent imaging. Results showed that BSA-LTB NPs presented a narrow size distribution with an average hydrodynamic diameter of approximately 254±19 nm and a mean zeta potential of approximately -19.95±0.94 mV. In addition, approximately 80.1% of drug was encapsulated in NPs and released in the biphasic pattern. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that BSA-LTB NPs exhibited higher cytotoxic activity than non-targeted NPs (BSA NPs) in SMMC-7721 cells. Fluorescent imaging results proved that, compared with BSA NPs, BSA-LTB NPs could greatly enhance cellular uptake. Hence, the results indicate that BSA-LTB NPs could be a potential nanocarrier to improve targeted delivery of 5-fluorouracil to tumor cells via mediation of LTB.

Keywords: heat-labile enterotoxin subunit B, nanoparticle, bovine serum albumin, 5-fluorouracil


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