title: Microfluidic fabrication of 6-methoxyethylamino numonafide-eluting magnetic microspheres.
abstract: Recently, 6-methoxyethylamino numonafide (MEAN) exhibited potent inhibition of hepatocellular carcinoma (HCC) cell growth and less systemic toxicity than amonafide. MEAN may serve as an ideal candidate for the treatment of HCC; however, liver-directed, selective infusion methods may be critical to maximize the MEAN dose delivered to the targeted tumors. This study describes the microfluidic fabrication of MEAN-eluting ultrasmall superparamagnetic iron oxide (USPIO) nanocluster-containing alginate microspheres (MEAN-magnetic microspheres) intended for selective transcatheter delivery to HCC. The resulting drug delivery platform was mono-disperse, microsphere sizes were readily controlled based on channel flow rates during synthesis procedures, and drug release rates from the microspheres could be readily controlled with the introduction of USPIO nanoclusters. The MR relaxivity properties of the microspheres suggest the feasibility of in vivo imaging after administration, and these microspheres exhibited potent therapeutic effects significantly inhibiting cell growth inducing apoptosis in hepatoma cells.
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA. Electronic address: dhkim@northwestern.edu.
authors.forename: D-H
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA.
authors.forename: T
authors.initials: T
authors.lastname: Choy
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine Chicago, IL 60611, USA.
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.affiliation: Division of Hepatology, Northwestern University Feinberg School of Medicine Chicago, IL 60611, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Green
authors.affiliation: Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Omary
authors.affiliation: Department of Radiology, Northwestern University, Chicago, IL 60611, USA; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA; Department of Electrical Engineering and Computer Science, Evanston, IL 60208, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA; Department of Biomedical Engineering, Northwestern University, Chicago, IL 60208, USA; International Institute of Nanotechnology (IIN), Northwestern University, Evanston, IL 60208, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Larson
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003911:Dextrans / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D060328:Magnetic Phenomena; D009682:Magnetic Resonance Spectroscopy; D058185:Magnetite Nanoparticles / Q000737:chemistry; D044085:Microfluidics / Q000379:methods*; D008863:Microspheres; D053644:Naphthalimides / Q000737:chemistry*; D010316:Particle Size
chemical_list: C562029:6-methoxyethylaminonumonafide; D003911:Dextrans; D058185:Magnetite Nanoparticles; D053644:Naphthalimides; C097921:ferumoxtran-10
keywords: Anticancer drug; Controlled drug release; Liver cancer; Magnetic microspheres; Microfluidics