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

• Published in: Journal of nanobiotechnology 2016-04, Vol.14 (1), p.32-32, Article 32
• Main Authors: Fasehee, Hamidreza, Dinarvand, Rassoul, Ghavamzadeh, Ardeshir, Esfandyari-Manesh, Mehdi, Moradian, Hanieh, Faghihi, Shahab, Ghaffari, Seyed Hamidollah
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Disulfiram - administration & dosage; Drug Carriers - administration & dosage; Female; Folate Receptors, GPI-Anchored - metabolism; Folic Acid - administration & dosage; Folic Acid - analogs & derivatives; Folic Acid - metabolism; Humans; Lactic Acid - administration & dosage; MCF-7 Cells; Nanoparticles - administration & dosage; Particle Size; Polyethylene Glycols - administration & dosage; Polyglycolic Acid - administration & dosage
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-016-0183-z

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. 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. The 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. 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.