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Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : Nanomedicine: Nanotechnology, Biology, and Medicine

Source : Nanomedicine: Nanotechnology, Biology, and Medicine (2013)

Url : http://www.scopus.com/inward/record.url?eid=2-s2.0-84886865776&partnerID=40&md5=2fedcd669f9eb184013c95f6d87dec95

Keywords : Acute, acute granulocytic leukemia, Acute myeloid leukemia, adult, apoptosis, article, Biological, biological model, Bone, bone marrow cell, cancer patient

Campus : Kochi

School : Center for Nanosciences

Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences

Department : Nanosciences, Nanosciences and Molecular Medicine

Year : 2013, 2014

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   100 nm 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. © 2013 Elsevier Inc. All rights reserved.

Cite this Research Publication : Pa Chandran, Kavalakatt, Aa, Malarvizhi, G. La, Vasanthakumari, D. R. V. Na, Retnakumari, A. Pa, Sidharthan, Nb, Pavithran, Kb, Nair, Sa, and Dr. Manzoor K., “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, 2013.

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