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Funcionalized Gold Nanoparticles as Potential New Treatment for Acute Myeloid Leukemia
Author(s) -
Gaiser AnnKathrin,
Hafner Susanne,
Schmiech Michael,
Syrovets Tatiana,
Simmet Thomas
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.925.5
Subject(s) - myeloid leukemia , daunorubicin , chemistry , cytotoxic t cell , cytarabine , leukemia , programmed cell death , colloidal gold , apoptosis , cancer research , myeloid , in vivo , biophysics , in vitro , medicine , biology , immunology , nanotechnology , materials science , biochemistry , nanoparticle , microbiology and biotechnology
Surface functionalization of nanoparticles is often used to target specific cell types or cellular organelles. We have previously found that positively charged nanoparticles manufactured from biologically inert polystyrene are highly cytotoxic towards acute myeloid leukemia cell lines while primary macrophages of healthy donors are resistant. Acute myeloid leukemia (AML) is a malignancy of the myeloid lineage of the hematopoietic system and, to date, the gold standard treatment combines two chemotherapeutic drugs ‐ cytarabine and daunorubicin. The prognosis and treatment outcome of AML strongly depends on the age of the patients. While patients younger than 65 years show a 5‐year overall survival rate of around 50%, older patients show a very poor 5‐year survival of only 4%. Hence, there is still a need for new agents with higher specificity towards AML cells and lower general cytotoxicity. In the current study we produced and characterized new amino‐functionalized gold nanoparticles and investigated their potential to target specifically leukemia cells, in vitro and in vivo . The amino‐functionalized gold nanoparticles (AuNP+) exhibit a positive surface charge, and, like the polystyrene particles, proved to be extremely cytotoxic towards AML cells. The type of cell death was identified to be apoptosis. Further analysis of the underlying mechanism revealed an early loss of mitochondrial functions, including inhibition of mitochondrial respiration and mitochondrial membrane permeabilization. Consequently, this led to release of cytochrome C into the cytosol and caspase activation. In contrast to positively charged AuNP+, non‐functionalized (AuNP) or carboxy‐functionalized gold nanoparticles with a negative surface charge (AuNP‐) did not show any cytotoxic effect. This differential toxicity of the gold nanoparticles might be due to higher uptake of positively charged AuNP+ particles by AML cells, as detected by transmission electron microscopy. The positively charged particles also induced cell death in primary human leukemia cells and reduced their colony‐forming potential, while healthy hematopoietic cells were not affected by treatment with AuNP+. Overall, we have found so far that our positively charged gold nanoparticles induce apoptosis and exhibit selective cytotoxicity towards AML cells. Further we aim to understand the cause of higher sensitivity of AML cells and to investigate the efficacy of AML treatment by AuNP+ particles in a mouse model engrafted with patient‐derived primary AML cells. Support or Funding Information VolkswagenStiftung