title: On-chip synthesis of fine-tuned bone-seeking hybrid nanoparticles.
abstract: OBJECTIVE
  Here we report a one-step approach for reproducible synthesis of finely tuned targeting multifunctional hybrid nanoparticles (HNPs).
  
  
  METHODS
  A microfluidic-assisted method was employed for controlled nanoprecipitation of bisphosphonate-conjugated poly(D,L-lactide-co-glycolide) chains, while coencapsulating superparamagnetic iron oxide nanoparticles and the anticancer drug Paclitaxel.
  
  
  RESULTS
  Smaller and more compact HNPs with narrower size distribution and higher drug loading were obtained at microfluidic rapid mixing regimen compared with the conventional bulk method. The HNPs were shown to have a strong affinity for hydroxyapatite, as demonstrated in vitro bone-binding assay, which was further supported by molecular dynamics simulation results. In vivo proof of concept study verified the prolonged circulation of targeted microfluidic HNPs. Biodistribution as well as noninvasive bioimaging experiments showed high tumor localization and suppression of targeted HNPs to the bone metastatic tumor.
  
  
  CONCLUSIONS
  The hybrid bone-targeting nanoparticles with adjustable characteristics can be considered as promising nanoplatforms for various theragnostic applications.
authors.affiliation: Parker H Petit Institute for Bioengineering & Bioscience, GW Woodruff School of Mechanical Engineering & School of Materials Science & Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0295, USA.|Laboratoire de Microsystemes (LMIS4), Institute of Microengineering & Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.|Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Hasani-Sadrabadi
authors.affiliation: Department of Developmental Sciences, Marquette University School of Dentistry, Milwaukee, WI 53201, USA.
authors.forename: Erfan
authors.initials: E
authors.lastname: Dashtimoghadam
authors.affiliation: Department of Engineering & Technology, Golestan University, AliabadKatool, Iran.
authors.forename: Ghasem
authors.initials: G
authors.lastname: Bahlakeh
authors.affiliation: Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.|Department of Bioengineering, University of California at Los Angeles, Los Angeles, CA 951600, USA.
authors.forename: Fatemeh S
authors.initials: FS
authors.lastname: Majedi
authors.affiliation: Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Keshvari
authors.affiliation: Laboratoire de Microsystemes (LMIS4), Institute of Microengineering & Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Jules J
authors.initials: JJ
authors.lastname: Van Dersarl
authors.affiliation: Laboratoire de Microsystemes (LMIS4), Institute of Microengineering & Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Bertsch
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Arash
authors.initials: A
authors.lastname: Panahifar
authors.affiliation: Laboratoire de Microsystemes (LMIS4), Institute of Microengineering & Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Renaud
authors.affiliation: Department of Developmental Sciences, Marquette University School of Dentistry, Milwaukee, WI 53201, USA.|Department of Engineering Science, University of Oxford, Oxford OX1 3PJ, UK.
authors.forename: Lobat
authors.initials: L
authors.lastname: Tayebi
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Division of Cardiovascular Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Morteza
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: Parker H Petit Institute for Bioengineering & Bioscience, GW Woodruff School of Mechanical Engineering & School of Materials Science & Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0295, USA.
authors.forename: Karl I
authors.initials: KI
authors.lastname: Jacob
mesh_terms: D004164:Diphosphonates / Q000737:chemistry*; D044085:Microfluidics / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D004164:Diphosphonates
keywords: bisphosphonate; bone targeting; hybrid nanoparticles; microfluidics platform; theragnosis