Pathway of cytotoxicity induced by folic acid modified selenium nanoparticles in MCF-7 cells
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BIOTECHNOLOGICAL PRODUCTS AND PROCESS ENGINEERING
Pathway of cytotoxicity induced by folic acid modified selenium nanoparticles in MCF-7 cells Jiang Pi & Hua Jin & RuiYing Liu & Bing Song & Qing Wu & Li Liu & JinHuan Jiang & Fen Yang & HuaiHong Cai & Jiye Cai
Received: 29 March 2012 / Revised: 7 August 2012 / Accepted: 9 August 2012 / Published online: 4 September 2012 # Springer-Verlag 2012
Abstract Selenium nanoparticles (Se NPs) have been recognized as promising materials for biomedical applications. To prepare Se NPs which contained cancer targeting methods and to clarify the cellular localization and cytotoxicity mechanisms of these Se NPs against cancer cells, folic acid protected/modified selenium nanoparticles (FA–Se NPs) were first prepared by a one-step method. Some morphologic and spectroscopic methods were obtained to prove the successfully formation of FA–Se NPs while free folate competitive inhibition assay, microscope, and several biological methods were used to determine the in vitro uptake, subcellular localization, and cytotoxicity mechanism of FA–Se NPs in MCF-7 cells. The results indicated that the 70-nm FA–Se NPs were internalized by MCF-7 cells through folate receptor-mediated endocytosis and targeted to mitochondria located regions through endocytic vesicles transporting. Then, the FA–Se NPs entered into mitochondria; triggered the mitochondriadependent apoptosis of MCF-7 cells which involved oxidative stress, Ca2+ stress changes, and mitochondrial dysfunction; and finally caused the damage of mitochondria. FA–Se NPs released from broken mitochondria were transported into nucleus and further into nucleolus which then induced MCF-7 cell cycle arrest. In addition, FA–Se NPs could induce cytoskeleton disorganization and induce MCF-7 cell membrane morphology alterations. These results collectively suggested Jiang Pi, Hua Jin, and RuiYing Liu contribute equally to this paper and share the first authorship. J. Pi : H. Jin : B. Song : L. Liu : J. Jiang : F. Yang : H. Cai : J. Cai (*) Department of Chemistry and Institute for Nano-Chemistry, Jinan University, Guangzhou, China e-mail: [email protected] R. Liu : Q. Wu The First Affiliated Hospital of Jinan University, Guangzhou, China
that FA–Se NPs could be served as potential therapeutic agents and organelle-targeted drug carriers in cancer therapy. Keywords Apoptosis . Endocytosis . Folate . MCF-7 cells . Selenium nanoparticles . Subcellular localization
Introduction Cancer is a great threat to public health, with more than 3.2 million new cases being diagnosed and more than 1.7 million patients lose their lives each year just in Europe (Milosavljevic et al. 2002). Most of cancer patients are suffering from the toxicity and side effect of chemotherapy (Stéphanie et al. 2011). The development of new drugs with high efficacy and high selectivity to cancer cells is more and more important. The trace mineral selenium (Se) is an essential nutrient of fundamental importance to human biology and involves a lot physiological functions. It has many import
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