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.
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.
School of Pharmacy, Liaoning Medical University, Jinzhou, People's Republic of China.
Liang
L
Zhao
Central Laboratory of Liaoning Medical University, Jinzhou, People's Republic of China.
Rongjian
R
Su
National Vaccine and Serum Institute, Beijing, People's Republic of China.
Wenyu
W
Cui
School of Pharmacy, Liaoning Medical University, Jinzhou, People's Republic of China.
Yijie
Y
Shi
School of Pharmacy, Liaoning Medical University, Jinzhou, People's Republic of China.
Liwei
L
Liu
School of Veterinary Medicine, Liaoning Medical University, Jinzhou, People's Republic of China.
Chang
C
Su
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004058:Diffusion; D004768:Enterotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D053769:Nanocapsules; D012710:Serum Albumin, Bovine; C027538:heat-labile enterotoxin, E coli; D005472:Fluorouracil
5-fluorouracil; bovine serum albumin; heat-labile enterotoxin subunit B; nanoparticle