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. Lastly, our results help elucidate nanomedicines’ in vivo fate and provide guidelines for efficient drug delivery.
- Authors:
-
- 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)
- Publication Date:
- Research Org.:
- 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 Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1258344
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 7; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 77 NANOSCIENCE AND NANOTECHNOLOGY
Citation Formats
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, and Mulder, Willem J. M. Augmenting drug–carrier compatibility improves tumour nanotherapy efficacy. United States: N. p., 2016.
Web. doi:10.1038/ncomms11221.
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. Augmenting drug–carrier compatibility improves tumour nanotherapy efficacy. United States. https://doi.org/10.1038/ncomms11221
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, and Mulder, Willem J. M. Wed .
"Augmenting drug–carrier compatibility improves tumour nanotherapy efficacy". United States. https://doi.org/10.1038/ncomms11221. https://www.osti.gov/servlets/purl/1258344.
@article{osti_1258344,
title = {Augmenting drug–carrier compatibility improves tumour nanotherapy efficacy},
author = {Zhao, Yiming and Fay, Francois and Hak, Sjoerd and Manuel Perez-Aguilar, Jose and Sanchez-Gaytan, Brenda L. and Goode, Brandon and Duivenvoorden, Raphael and de Lange Davies, Catharina and Bjorkoy, Astrid and Weinstein, Harel and Fayad, Zahi A. and Perez-Medina, Carlos and Mulder, Willem J. M.},
abstractNote = {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.},
doi = {10.1038/ncomms11221},
journal = {Nature Communications},
number = ,
volume = 7,
place = {United States},
year = {Wed Apr 13 00:00:00 EDT 2016},
month = {Wed Apr 13 00:00:00 EDT 2016}
}
Web of Science
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