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

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.

Effects of Desolvating Agent Types, Ratios, and Temperature on Size and Nanostructure of Nanoparticles from α‐Lactalbumin and Ovalbumin

“…For OVA nanoparticles, the ζ potentials were around −20 mV, suggesting the possibility for aggregation to occur over time. Our findings are consistent with the ζ potential observed with other biopolymeric nanoparticles (Zhao and others ; Veilleux and others ).…”

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

“…237 LTB binds specifically to the monosialoganglioside GM1 which is the host receptor of LT. 236 A novel NP was developed utilizing a mixture of LTB and BSA for HCC-targeted delivery of 5-FU. 238 Investigation on SMMC-7721 cells showed enhanced cytotoxicity and cellular uptake of BSA-LTB NPs compared with BSA NPs, suggesting the promising targeting efficiency of LTB.…”

Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance

“…Annexin V-FITC/propidium iodide staining assay was performed and the apoptotic and necrotic cells were quantified by flow cytometry. According to the protocol of our previous study, 44 free gefitinib, gefitinib and shMDR1, gefitinib NPs, gefitinib NPs combined with shMDR1 NPs, and shMDR1/gefitinib NPs with the same concentration of gefitinib were used to treat gefitinib-resistant Hela cells for 48 hours at 37°C for further analysis.…”