title: Design of FLT3 Inhibitor - Gold Nanoparticle Conjugates as Potential Therapeutic Agents for the Treatment of Acute Myeloid Leukemia.
abstract: BACKGROUND
  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 specifically, at the tumor site.
  
  
  RESULTS
  FLT3 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences and Faculty of Physics, Babes-Bolyai University, T. Laurian 42, 400271, Cluj-Napoca, Romania. timea.simon@ubbcluj.ro.
authors.forename: Timea
authors.initials: T
authors.lastname: Simon
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Bulevardul 21 Decembrie 1918 Nr 73, 400124, Cluj-Napoca, Romania. ciprian.tomuleasa@gmail.com.|Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Marinescu Street 23, 40015, Cluj-Napoca, Romania. ciprian.tomuleasa@gmail.com.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Tomuleasa
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Bulevardul 21 Decembrie 1918 Nr 73, 400124, Cluj-Napoca, Romania. ancasbojan@yahoo.ca.
authors.forename: Anca
authors.initials: A
authors.lastname: Bojan
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Marinescu Street 23, 40015, Cluj-Napoca, Romania. ioananeagoe29@gmail.com.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ioananeagoe29@gmail.com.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
authors.affiliation: Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences and Faculty of Physics, Babes-Bolyai University, T. Laurian 42, 400271, Cluj-Napoca, Romania. sanda.boca@phys.ubbcluj.ro.
authors.forename: Sanda
authors.initials: S
authors.lastname: Boca
authors.affiliation: Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences and Faculty of Physics, Babes-Bolyai University, T. Laurian 42, 400271, Cluj-Napoca, Romania. simion.astilean@phys.ubbcluj.ro.
authors.forename: Simion
authors.initials: S
authors.lastname: Astilean
keywords: Acute myeloid leukemia; Drug-loaded gold nanoparticles; FLT3 inhibitors; Pluronic