Abstract
BackgroundA folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied.ResultsThe folate-receptor-targeted nanoparticles are internalized into the cells, induce reactive oxygen species formation, induce apoptosis and inhibit cell proliferation more efficiently compared to the untargeted nanoparticles. The acute and toxicity test show the maximum dose of disulfiram equivalent of nanoparticles for intra-venous injection is 6 mg/kg while show significant decrease in the breast cancer tumor growth rate.ConclusionIt is believed that the developed formulation could be used as a potential vehicle for successful delivery of disulfiram, an old and inexpensive drug, into breast cancer cells and other solid tumors.Graphical abstractDisulfiram, an old and inexpensive drug, is encapsulated in folate-targeted PLGA-PEG nanoparticles and delivered into breast cancer cells using passive and active targeting to inhibit tumor growth in mice
Highlights
A folate-receptor-targeted poly (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells
MO, USA); disulfiram, methylene chloride, diethyl ether, methanol and dimethyl sulfoxide (DMSO) was obtained from Merck (Darmstadt, Germany); Fetal bovine serum (FBS), DMEM media, phosphate-buffered saline (PBS) buffer, Trypsin/ EDTA and penicillin–streptomycin were purchased from GIBCO (Maryland, USA); MTT (3-(4,5-dimethylthiazol2-yl)-2,5- diphenyltetrazolium bromide) assay kit was obtained from Roche (Mannhein, Germany)
The presence of amide bond C = O stretch) between PLGA-PEG and PEG-folate linkages were observed at 1630 cm−1
Summary
A folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied. During the last few years, a growing body of evidence from both in vivo and in vitro studies indicated that disulfiram has anticancer properties [2]. Fasehee et al J Nanobiotechnol (2016) 14:32 of DS is copper (Cu) dependent [11]. It means that the redox conversion of disulfiram is specific to Cu (II) and no other biological metal ions such as Fe (II or III) and Mn(III) [19]. It could be degraded into diethyldithiocarbamate (DDTC) during the absorption into the blood stream [4, 12]
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