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

Journal of Nanobiotechnology

Research

Mehdi Esfandyari-Manesh¹  Ardeshir Ghavamzadeh²  Seyed Hamidollah Ghaffari²  Rassoul Dinarvand³  Hamidreza Fasehee⁴  Shahab Faghihi⁴  Hanieh Moradian⁵ 

[1] Department of Chemistry, Amirkabir University of Technology, Tehran, Iran;Hematology, Oncology and Stem cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran;Nanotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran;Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), 14965/161, Tehran, Iran;Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology (NIGEB), 14965/161, Tehran, Iran;Faculty of Biomedical Engineering, Amirkabir University of Technology, 15875/4413, Tehran, Iran;

关键词: Disulfiram;    PLGA nanoparticles;    Folate receptor;    Breast cancer cells;    Apoptosis;    Targeted drug delivery;   

DOI  :  10.1186/s12951-016-0183-z

 received in 2016-01-26, accepted in 2016-04-07,  发布年份 2016

来源: Springer

【 摘 要 】

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

【 授权许可】

CC BY   
© Fasehee et al. 2016