Publication Type:

Journal Article

Source:

Nanomedicine: Nanotechnology, Biology, and Medicine, Elsevier Inc., Volume 10, Number 4, p.721-732 (2014)

URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84900344487&partnerID=40&md5=c0df5ee71735abaa9323442cab7c6dd6

Keywords:

Acute, acute granulocytic leukemia, Acute myeloid leukemia, adult, apoptosis, article, Biological, biological model, Bone, bone marrow cell, cancer patient, cancer recurrence, CD34 antigen, CD38 antigen, cell assay, Cell culture, cell cycle arrest, Cell death, cell proliferation, Cell-cycle arrest, child, clinical article, clonogenesis, computer model, Computer simulation, controlled study, cytotoxicity, Diseases, Drug effects, drug sensitivity, enzyme activity, enzyme inhibition, Epigenesis, epigenetics, female, gene expression, gene mutation, Genetic, genetic epigenesis, genetics, HDAC inhibitions, Heterogeneous populations, histone deacetylase, histone deacetylase inhibitor, Histone Deacetylase Inhibitors, HL 60 cell line, HL-60 Cells, human, human cell, human serum albumin, Humans, hydroxamic acid, Hydroxamic Acids, in vitro study, Leukemia, male, Medical nanotechnology, metabolism, middle aged, Models, Myeloid, myeloid leukemia cell line, Nano-vorinostat, nanomedicine, oxidation, pathology, phenotype, physical chemistry, procedures, promyelocytic leukemia, Proteins, Refractory materials, school child, stem cell, Stem cell phenotypes, Stem cells, Therapeutic strategy, vorinostat

Abstract:

Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n=9), including refractory and relapsed cases, and three representative cell lines expressing CD34+/CD38- stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having  100nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML. From the Clinical Editor: Through the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia. © 2014 Elsevier Inc.

Notes:

cited By 2

Cite this Research Publication

, “Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases”, Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 10, pp. 721-732, 2014.