Augmenting drug–carrier compatibility improves tumour nanotherapy efficacy

Zhao, Yiming; Fay, Francois; Hak, Sjoerd; Manuel Perez-Aguilar, Jose; Sanchez-Gaytan, Brenda L.; Goode, Brandon; Duivenvoorden, Raphael; de Lange Davies, Catharina; Bjorkoy, Astrid; Weinstein, Harel; Fayad, Zahi A.; Perez-Medina, Carlos; Mulder, Willem J. M.

doi:10.1038/ncomms11221

Title: Augmenting drug–carrier compatibility improves tumour nanotherapy efficacy

Journal Article · Wed Apr 13 00:00:00 EDT 2016 · Nature Communications

DOI:https://doi.org/10.1038/ncomms11221· OSTI ID:1258344

Zhao, Yiming ^[1]; Fay, Francois ^[2]; Hak, Sjoerd ^[3]; Manuel Perez-Aguilar, Jose ^[4]; Sanchez-Gaytan, Brenda L. ^[1]; Goode, Brandon ^[1]; Duivenvoorden, Raphael ^[5]; de Lange Davies, Catharina ^[3]; Bjorkoy, Astrid ^[3]; Weinstein, Harel ^[6]; Fayad, Zahi A. ^[1]; Perez-Medina, Carlos ^[1]; Mulder, Willem J. M. ^[5]

Icahn School of Medicine at Mount Sinai, New York, NY (United States)
IcaIcahn School of Medicine at Mount Sinai, New York, NY (United States)
The Norwegian Univ. of Science and Technology, Trondheim, (Norway)
Weill Cornell Medical College of Cornell Univ., New York, NY (United States); IBM Thomas J. Watson Research Center, Yorktown Heights, NY (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States); Academic Medical Center, Amsterdam (The Netherlands)
Weill Cornell Medical College of Cornell Univ., New York, NY (United States)

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. Lastly, our results help elucidate nanomedicines’ in vivo fate and provide guidelines for efficient drug delivery.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); UT-Battelle LLC/ORNL, Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1258344

Journal Information:: Nature Communications, Vol. 7; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 126 works

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