Novel green synthesis of Hibiscus sabdariffa flower extract conjugated gold nanoparticles with excellent anti‐acute myeloid leukemia effect in comparison to daunorubicin in a leukemic rodent model

2019 ◽  
Vol 34 (1) ◽  
Author(s):  
Mohammad Mahdi Zangeneh ◽  
Akram Zangeneh
Keyword(s):  
Gold Nanoparticles ◽  
Acute Myeloid Leukemia ◽  
Green Synthesis ◽  
Myeloid Leukemia ◽  
Rodent Model ◽  
Hibiscus Sabdariffa ◽  
Flower Extract ◽  
Acute Myeloid

Gelatin-coated Gold Nanoparticles as Carriers of FLT3 Inhibitors for Acute Myeloid Leukemia Treatment

2016 ◽  
Vol 87 (6) ◽  
pp. 927-935 ◽  
Author(s):  
Sorina Suarasan ◽  
Timea Simon ◽  
Sanda Boca ◽  
Ciprian Tomuleasa ◽  
Simion Astilean
Keyword(s):  
Gold Nanoparticles ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Flt3 Inhibitors ◽  
Leukemia Treatment ◽  
Acute Myeloid

scholarly journals Drug-DNA Conjugated Gold Nanoparticles for the Treatment of Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4935-4935
Author(s):  
Nathan Gossai ◽  
Jordan Naumann ◽  
Ed Zamora ◽  
Nan-Sheng Li ◽  
Joseph Piccirilli ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Acute Myeloid Leukemia ◽  
T Cell Activation ◽  
Myeloid Leukemia ◽  
Cell Activation ◽  
Leukemia Cell ◽  
Leukemia Cells ◽  
Cd34 Cells ◽  
Acute Myeloid ◽  
Novel Therapeutic

Abstract INTRODUCTION: Novel therapies are needed for acute myeloid leukemia as only ~60% of children are cured despite maximally intensive cytotoxic chemotherapy. Functionalized gold nanoparticles (AuNP) are utilized for many biomedical applications and represent a potentially novel therapeutic approach in leukemia. We enhanced this technology by developing an AuNP system that selectively releases molecularly targeted drugs in leukemia cells. METHODS: AuNPs were functionalized with short, double-stranded oligonucleotides with sequence complementarity to genes overexpressed in or unique to a leukemia cell (e.g. survivin or AML/ETO). Only the anti-sense oligonucleotide is covalently bound to the nanoparticle via a thiol linker. Thus, after entering leukemia cells, the endogenous targeted oncogene mRNA can bind to its complementary sequence on the AuNP and displace the non-covalently bound oligonucleotide which, in our system, is conjugated to the multi-tyrosine kinase inhibitor dasatinib. As a binary reaction, the amount of dasatinib-conjugated oligonucleotide released from the nanoparticle is directly proportional to both the presence and abundance of the complementary mRNA present in a cell. We evaluated AuNP uptake into multiple AML cell lines, as well as normal hematopoietic cells. The effect of dasatinib-AuNPs on dasatinib-sensitive leukemia cell lines was evaluated using proliferation assays, annexin V staining, and cell colony assays. Toxicity in T-cells and CD34+ cells was assessed with T-cell activation and p-SRC assays, respectively. RESULTS: Conjugation of dasatinib to an oligonucleotide complementary to a region of the survivin gene did not perturb its ability to inhibit SRC and c-KIT kinases in vitro. Leukemia cells demonstrate highly efficient AuNP uptake when cultured alone or with up to a 100-1000 fold excess of normal bone marrow cells. Treatment of K562 leukemia cells, containing a BCR/ABL translocation and high levels of survivin mRNA, with dasatinib-AuNPs resulted in dose-dependent p-SRC and p-CRKL inhibition. Furthermore, K562 cells also showed significantly impaired proliferation, increased apoptosis, and formed fewer colonies in methylcellulose. Conversely, normal T-cells and CD34+ cells, which express less survivin than leukemia cells, were significantly less affected by dasatinib-AuNPs than dasatinib alone as measured by T-cell activation assays and p-SRC levels, respectively. CONCLUSIONS: This method of using functionalized AuNPs to deliver and activate dasatinib in leukemia cells augments drug efficacy while minimizing toxicity and thus represents a novel therapeutic strategy for AML. Ongoing work is underway to characterize the mechanism of preferential AuNP uptake in leukemia cells and assessing in vivo activity using a murine xenotransplantation model of leukemia. Disclosures No relevant conflicts of interest to declare.

Targeting epigenetic pathway with gold nanoparticles for acute myeloid leukemia therapy

Biomaterials ◽  
2018 ◽  
Vol 167 ◽  
pp. 80-90 ◽  
Author(s):  
Rong Deng ◽  
Na Shen ◽  
Yang Yang ◽  
Hongliang Yu ◽  
Shuping Xu ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Myeloid
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