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Revision as of 09:05, 3 March 2020
Gaiser A, Hafner S, Schmiech M, Bรผchele B, Schรคfer P, Arnim CA, Calzia, E, FeuringโBuske M, Buske C, Vick B, Jeremias I, Syrovets T, Simmet T (2019) Gold nanoparticles with selective antileukemic activity in vitro and in vivo target mitochondrial respiration. Adv Ther (Weinh) doi:10.1002/adtp.201800149. |
ยป Open Access
Gaiser A, Hafner S, Schmiech M, Buechele B, Schaefer P, Arnim CA, Calzia E, FeuringโBuske M, Buske C, Vick B, Jeremias I, Syrovets T, Simmet T (2019) Adv Ther (Weinh)
Abstract: This study explores biocompatible aminoโfunctionalized gold nanoparticles (AuโNH2) as nanotherapeutics for the selective eradication of leukemia cells, elucidates the mechanism of cytotoxicity, and it confirms in vivo efficacy of the engineered nanomaterial. AuโNH2 trigger apoptotic cell death of myeloid leukemia cell lines and primary acute myeloid leukemia (AML) cells by i) inhibition of mitochondrial respiration, ii) ATP depletion, iii) loss of mitochondrial membrane potential, and iv) mitochondrial release of cytochrome c. AuโNH2 act selectively on leukemia cells inasmuch as the viability of normal peripheral blood mononuclear cells and macrophages as well as the colony formation of hematopoietic stem cells remain basically unaffected. The selectivity of AuโNH2 for AML cells can be attributed to both the preferential accumulation of AuNH2 in AML cells and the strong dependence of those cells on mitochondrial oxidative phosphorylation for ATP production. Importantly, AuโNH2 applied either as monotherapy or as a cytarabine combination regimen possess antileukemic efficacy in the absence of adverse events in mice xenografted with primary human AML in vivo. The engineered material may pave the way for a novel nanotherapeutic treatment of AML.
โข Bioblast editor: Plangger M โข O2k-Network Lab: DE Ulm Radermacher P
Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology
Pathology: Cancer
Organism: Human Tissue;cell: Blood cells Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET
Pathway: ROX
HRR: Oxygraph-2k
Labels, 2019-03, PBMC, Leukemia