Gold Nanoparticles with Selective Antileukemic Activity In Vitro and In Vivo Target Mitochondrial Respiration

Gaiser, Ann-Kathrin; Hafner, Susanne; Schmiech, Michael; Buchele, Berthold; Schafer, Patrick; Arnim, Christine A. von; Calzia, Enrico; Feuring-Buske, Michaela; Buske, Christian; Vick, Binje; Jeremias, Irmela; Syrovets, Tatiana und Simmet, Thomas (2019): Gold Nanoparticles with Selective Antileukemic Activity In Vitro and In Vivo Target Mitochondrial Respiration. In: Advanced Therapeutics, Bd. 2, Nr. 6, UNSP 1800149

Abstract

This study explores biocompatible amino-functionalized gold nanoparticles (Au-NH2) as nanotherapeutics for the selective eradication of leukemia cells, elucidates the mechanism of cytotoxicity, and it confirms in vivo efficacy of the engineered nanomaterial. Au-NH2 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. Au-NH2 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 Au-NH2 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, Au-NH2 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch