Augmenting drug–carrier compatibility improves tumour nanotherapy efficacy

Yiming Zhao, François Fay, Sjoerd Hak, Jose Manuel Perez-Aguilar, Brenda L. Sanchez-Gaytan, Brandon Goode, Raphaël Duivenvoorden, Catharina de Lange Davies, Astrid Bjørkøy, Harel Weinstein, Zahi A. Fayad, Carlos Pérez-Medina and Willem J. M. Mulder ()
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Yiming Zhao: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai
François Fay: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai
Sjoerd Hak: The Norwegian University of Science and Technology
Jose Manuel Perez-Aguilar: Weill Cornell Medical College of Cornell University
Brenda L. Sanchez-Gaytan: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai
Brandon Goode: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai
Raphaël Duivenvoorden: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai
Catharina de Lange Davies: The Norwegian University of Science and Technology
Astrid Bjørkøy: The Norwegian University of Science and Technology
Harel Weinstein: Weill Cornell Medical College of Cornell University
Zahi A. Fayad: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai
Carlos Pérez-Medina: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai
Willem J. M. Mulder: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11221

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