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

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.

Emerging Nanopharmaceuticals and Nanonutraceuticals in Cancer Management

“…The results of the in vivo study indicated that nanocarriers can significantly and selectively facilitate tumor reduction [86]. Similar promising results were also shown in other studies, for example in the use of docetaxel nano-targeted delivery for the treatment of prostate cancer, use of NDAT for the targeted delivery of paclitaxel, cisplatin, and doxorubicin in tumor xenografts and in the delivery of toremifene in prostate cancer [87][88][89][90][91].…”

“…Active nano-targeting for tumor-targeted delivery could be achieved using high-affinity ligand for a unique target that is overexpressed by cancer cells and their associated microenvironment, such as the case with integrin αvβ3, PSMA, or CD44 for delivery of chemotherapy into specific tumors [85][86][87][88][89][90][91]. Nanotechnology has been studied in vitro and in vivo to potentially restrict the action of the anti-angiogenic agent, diamino tetraiodothyroacetic acid (DAT) to the integrin avβ3 by conjugating DAT to PLGA NPs, forming DAT-conjugated PLGA (NDAT).…”

Boswellia dalzielii-Mediated Silver Nanoparticles Inhibited Acute Myeloid Leukemia (AML) Kasumi-1 Cells by Inducing Cell Cycle Arrest

“…Silver nanoparticles synthesized from Moringa oleifera leaf extract inhibited AML Kasumi-1 cell growth with IC50 of 7.5 μ g/ml after 72-hour treatment [ 46 ]. Furthermore, PLGA-antiCD44-PTL nanoparticles inhibited the Kasumi-1 leukemic cells by decreasing its viability by 40% [ 47 ]. In addition, Li et al [ 48 ] reported that CD33-targeted lipid nanoparticles (aCD33LNs) they synthesized effectively delivered GTI-2040 to the intended target to inhibit the proliferation of Kasumi-1 cells.…”

Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies

“…Besides new derivatives of PN with better bioavailability, alternative delivering systems are in the focus of current research. Encapsulation into the micelles, drug-loaded nano-vectors or nanographene delivery [16,[203][204][205][206] might allow to exploit the full spectrum of the anticancer activities of PN and may be crucial for the development of new combination therapies.…”