title: Augmenting drug-carrier compatibility improves tumour nanotherapy efficacy.
abstract: A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug-carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug-carrier compatibility affects drug release in a tumour mouse model. We found the drug's hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, we applied these findings to improve chemotherapeutic delivery by augmenting the parent drug's compatibility; as a result, we achieved better antitumour efficacy. Our results help elucidate nanomedicines' in vivo fate and provide guidelines for efficient drug delivery.
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: François
authors.initials: F
authors.lastname: Fay
authors.affiliation: Department of Circulation and Medical Imaging, The Norwegian University of Science and Technology, 7030 Trondheim, Norway.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Hak
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York 10065, USA.|IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Manuel Perez-Aguilar
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Sanchez-Gaytan
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Goode
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Duivenvoorden
authors.affiliation: Department of Physics, The Norwegian University of Science and Technology, 7030 Trondheim, Norway.
authors.forename: Catharina
authors.initials: C
authors.lastname: de Lange Davies
authors.affiliation: Department of Physics, The Norwegian University of Science and Technology, 7030 Trondheim, Norway.
authors.forename: Astrid
authors.initials: A
authors.lastname: Bjørkøy
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York 10065, USA.|The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, New York 10065, USA.
authors.forename: Harel
authors.initials: H
authors.lastname: Weinstein
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Medina
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.|Department of Medical Biochemistry, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008853:Microscopy; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D019265:Spectroscopy, Near-Infrared; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin