Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy

Abstract

Background and aims Every year, in Europe, acute myeloid leukemia (AML) is diagnosed in thousands of adults. For most subtypes of AML, the backbone of treatment was introduced nearly 40 years ago as a combination of cytosine arabinoside with an anthracycline. This therapy is still the worldwide standard of care. Two-thirds of patients achieve complete remission, although most of them ultimately relapse. Since the FLT3 mutation is the most frequent, it serves as a key molecular target for tyrosine kinase inhibitors (TKIs) that inhibit FLT3 kinase. In this study, we report the conjugation of TKIs onto spherical gold nanoparticles. Materials and methods The internalization of TKI-nanocarriers was proved by the strongly scattered light from gold nanoparticles and was correlated with the results obtained by transmission electron microscopy and dark-field microscopy. The therapeutic effect of the newly designed drugs was investigated by several methods including cell counting assay as well as the MTT assay. Results We report the newly described bioconjugates to be superior when compared with the drug alone, with data confirmed by state-of-the-art analyses of internalization, cell biology, gene analysis for FLT3-IDT gene, and Western blotting to assess degradation of the FLT3 protein. Conclusion The effective transmembrane delivery and increased efficacy validate its use as a potential therapeutic.

Nuclear MET requires ARF and is inhibited by carbon nanodots through binding to phospho-tyrosine in prostate cancer

“…Most importantly, we provided experimental, conceptual and promising novel treatment avenue that using c-dots to enhance RTK inhibitor efficiency, which is the first report in the green carbon-drug field, though there is a report using gold nanoparticles conjugated with FLT3 kinase inhibitor in leukemia (41). Thus green carbon nanoparticles would provide a more ecologically benefit treatment for combinatorial therapy or drug delivery using RTK inhibitors.…”

Nanoplasmonic Nanorods/Nanowires from Single to Assembly: Syntheses, Physical Mechanisms and Applications

“…where x is the electron position, m is the electron mass, g is the damping constant, e is the charge of the electron, E 0 is the external electric field amplitude, and w is the circular frequency of the external electric field. The expression for the oscillation of the electron can be described as x w; t ð Þ ¼ x 0 w ð Þexp À iwt ð Þ, by combining this relationship with equation (1), the expression of the induced dipole moment of the electron in the external electric field can be obtained as,…”

“…These nanomaterials can be produced by metals, semiconductors, inorganic materials, and metal nanostructures have many plasmonic and optical properties, such as the characteristics of light absorption, nonlinear optics, and unique surface plasmon resonance. [1] Among the noble metal nanomaterials, the chemical inertness and low resistivity of gold, the good electrical and thermal conductivity of silver have attracted much attention and research. In 1857, Michael Faraday proposed that gold microparticles can scatter light, which is called Faraday-Tyndall effect.…”

Nanoparticles—Emerging Potential for Managing Leukemia and Lymphoma

“…Inside the cells, the target gene mRNA binds to the antisense oligonucleotide and releases the drug-conjugated DNA oligonucleotide proportionally to level of BIRC5 mRNA in those cells (Gossai et al, 2014 ). Other studies examined the in vitro efficacy of drug-coated AuNPs on AML treatment improvement using TKIs and fludarabine (Simon et al, 2015 ; Petrushev et al, 2016 ; Song et al, 2016 ). One of these systems took additional advantage of folate grafted to the NPs’ surface.…”