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Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia

1
Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
2
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA
3
Clinical Hematology Unit, Mansoura University Oncology Center, Mansoura University, Mansoura 35516, Egypt
4
Fellow of Biochemistry Emergency Hospital, Mansoura University, Mansoura 35516, Egypt
*
Author to whom correspondence should be addressed.
Academic Editor: Alejandro Baeza
Molecules 2019, 24(11), 2103; https://doi.org/10.3390/molecules24112103
Received: 3 May 2019 / Revised: 24 May 2019 / Accepted: 29 May 2019 / Published: 3 June 2019
(This article belongs to the Special Issue Nanomaterials for Cancer Diagnosis and Therapy)
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Abstract

The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 µM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML. View Full-Text
Keywords: AML; nanoparticles with antiCD44 and encapsulating parthenolide; targeted therapy; nanoparticles; poly lactide co-glycolide AML; nanoparticles with antiCD44 and encapsulating parthenolide; targeted therapy; nanoparticles; poly lactide co-glycolide
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Darwish, N.H.E.; Sudha, T.; Godugu, K.; Bharali, D.J.; Elbaz, O.; El-ghaffar, H.A.A.; Azmy, E.; Anber, N.; Mousa, S.A. Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia. Molecules 2019, 24, 2103.

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