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.
Highlights
Releasing 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
Synthesis and Characterization of FMS-like tyrosine kinase 3 (FLT3) Inhibitor - Gold Nanoparticle conjugates The strategy employed for conjugating FLT3 inhibitors onto gold nanoparticle (GNP) implies the using of Pluronic F127 block copolymer as overall coating surface
Pluronic is an amphiphilic polymer composed of hydrophobic poly(propylene oxide) chains at the core and hydrophilic poly(ethylene oxide) chains at the ends arranged in a A-B-A structure (Fig. 1)
Summary
Releasing 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 at the tumor site. Acute myeloid leukemia (AML) is one of the most common and deadly leukemias worldwide [1,2,3]. By designing specific delivery systems or nano-carriers, higher drug concentrations can be transported to the malignant cell [10,11,12]. Related to acute myeloid leukemia, binding anti-FLT3 inhibitor drugs to nanocarriers might offer a new and exciting approach to an improved treatment. No data has been published related to the possibility to bind gold nanostructures or
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