Delivery of disulfiram into breast cancer cells using folate-receptor-targeted PLGA-PEG nanoparticles: in vitro and in vivo investigations

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

pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery

“…In this study, we developed pH-responsive VLNPs that can store DOX and possess a sustained-release property under tumour-associated conditions. A tumour-targeting ligand, FA, was therefore conjugated to the tHBcAg nanoparticles because it interacts strongly with the FR, which is highly expressed on the surface of many cancer cells, including colorectal cancer cells162531.…”

“…Displaying folic acid (FA) on VLNPs is a popular strategy to enhance specific uptake by tumour cells through folate receptor (FR)-mediated endocytosis1516. However, conjugation of FA directly onto VLNPs may cause inaccessibility of FA molecules to the FR17.…”

Repurposing disulfiram for cancer therapy via targeted nanotechnology through enhanced tumor mass penetration and disassembly

“…As a consequence, DSF can only kill a fraction of cancer cells, which probably is the main cause for the failure of several clinical trials involved with DSF. To address these issues, several DSF loaded nanoparticles have been developed to deliver DSF to tumor sites [19–22]. Nanoparticles can improve DSF solubility, isolate it from labile environment and enhance its accumulation in the tumor tissue, which altogether result in a better anticancer efficacy.…”

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“…It 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 169 .…”