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


RESULTS
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.


CONCLUSIONS
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.
Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 14965/161, Iran.
Hamidreza
H
Fasehee
Nanotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Rassoul
R
Dinarvand
Hematology, Oncology and Stem cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran.
Ardeshir
A
Ghavamzadeh
Department of Chemistry, Amirkabir University of Technology, Tehran, Iran.
Mehdi
M
Esfandyari-Manesh
Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 14965/161, Iran.|Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran, 15875/4413, Iran.
Hanieh
H
Moradian
Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 14965/161, Iran. sfaghihi@nigeb.ac.ir.
Shahab
S
Faghihi
Hematology, Oncology and Stem cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran. Shghaffari200@yahoo.com.
Seyed Hamidollah
SH
Ghaffari
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004221:Disulfiram / Q000008:administration & dosage*; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D005492:Folic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; C552831:poly(ethylene glycol)-folate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D005492:Folic Acid; D004221:Disulfiram
Apoptosis; Breast cancer cells; Disulfiram; Folate receptor; PLGA nanoparticles; Targeted drug delivery