Design of FLT3 Inhibitor - Gold Nanoparticle Conjugates as Potential Therapeutic Agents for the Treatment of Acute Myeloid Leukemia

Abstract

BackgroundReleasing drug molecules at the targeted location could increase the clinical outcome of a large number of anti-tumor treatments which require low systemic damage and low side effects. Nano-carriers of drugs show great potential for such task due to their capability of accumulating and releasing their payload specifically, at the tumor site.ResultsFLT3 inhibitor - gold nanoparticle conjugates were fabricated to serve as vehicles for the delivery of anti-tumor drugs. Lestaurtinib, midostaurin, sorafenib, and quizartinib were selected among the FLT3 inhibitor drugs that are currently used in clinics for the treatment of acute myeloid leukemia. The drugs were loaded onto nanoparticle surface using a conjugation strategy based on hydrophobic-hydrophobic interactions with the Pluronic co-polymer used as nanoparticle surface coating. Optical absorption characterization of the particles in solution showed that FLT3 inhibitor-incorporated gold nanoparticles were uniformly distributed and chemically stable regardless of the drug content. Drug loading study revealed a high drug content in the case of midostaurin drug which also showed increased stability. Drug release test in simulated cancer cell conditions demonstrated more than 56 % release of the entrapped drug, a result that correlates well with the superior cytotoxicity of the nano-conjugates comparatively with the free drug.ConclusionsThis is a pioneering study regarding the efficient loading of gold nanoparticles with selected FLT3 inhibitors. In vitro cytotoxicity assessment shows that FLT3-incorporated gold nanoparticles are promising candidates as vehicles for anti-tumor drugs and demonstrate superior therapeutic effect comparatively with the bare drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-015-1154-2) contains supplementary material, which is available to authorized users.

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.…”

The new era of nanotechnology, an alternative to change cancer treatment

“… 21 A wide range of anti-cancer drugs such as rituximab, lestauritinib, carboplatin, paclitaxel, doxorubicin and tyrosine kinase inhibitors have been loaded onto nanoparticles with a potential effect against various cancers, and a superior therapeutic efficacy than free chemotherapeutics. 22 – 26 …”

Development and Characterization of FLT3-Specific Curcumin-Loaded Polymeric Micelles as a Drug Delivery System for Treating FLT3-Overexpressing Leukemic Cells

“…43 Although there are numerous FLT3 inhibitors and antibodies that have been developed since the last decade, only a small number of FLT3-specific nanoparticles were reported. 44 According to anti-leukemia properties of CM on FLT3-overexpressing leukemic cells 16 and the effectiveness of drug delivery system (DDS) with target-specific nanoparticles, this study aims to produce FLT3-CM-micelles with surface FLT3-specific peptides, evaluate their properties, and investigate their cytotoxic effect on FLT3-overexpressing leukemic cell lines.…”