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 04:00:00 UTC 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. ^[5]; Goode, Brandon ^[5]; Duivenvoorden, Raphael ^[6]; de Lange Davies, Catharina ^[3]; Bjorkoy, Astrid ^[3]; Weinstein, Harel ^[7]; Fayad, Zahi A. ^[5]; Perez-Medina, Carlos ^[5]; Mulder, Willem J. M. ^[6]

Icahn School of Medicine at Mount Sinai, New York, NY (United States); Academic Medical Center, AZ, Amsterdam, (The Netherlands). Department of Medical Biochemistry
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)
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, Oak Ridge, TN (United States)

Sponsoring Organization:: DOE Office of Science; USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1258344

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

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Therapeutic targeting of trained immunity Mulder, Willem J. M.; Ochando, Jordi; Joosten, Leo A. B. Nature Reviews Drug Discovery, Vol. 18, Issue 7 https://doi.org/10.1038/s41573-019-0025-4	journal	April 2019
Facile dynamic one-step modular assembly based on boronic acid-diol for construction of a micellar drug delivery system Zhao, Zekai; Zhang, Ying; Tian, Chunli Biomaterials Science, Vol. 6, Issue 10 https://doi.org/10.1039/c8bm00712h	journal	January 2018
Investigating supramolecular systems using Förster resonance energy transfer Teunissen, Abraham J. P.; Pérez-Medina, Carlos; Meijerink, Andries Chemical Society Reviews, Vol. 47, Issue 18 https://doi.org/10.1039/c8cs00278a	journal	January 2018
In situ real-time tracing of hierarchical targeting nanostructures in drug resistant tumors using diffuse fluorescence tomography Guo, Qianqian; Wang, Yangyun; Zhang, Limin Chemical Science, Vol. 10, Issue 34 https://doi.org/10.1039/c9sc01841g	journal	January 2019
Modular lipid nanoparticle platform technology for siRNA and lipophilic prodrug delivery van der Meel, Roy; Chen, Sam; Zaifman, Josh Small https://doi.org/10.1101/2020.01.16.907394	journal	January 2020
Inhalation of peptide-loaded nanoparticles improves heart failure Miragoli, Michele; Ceriotti, Paola; Iafisco, Michele Science Translational Medicine, Vol. 10, Issue 424 https://doi.org/10.1126/scitranslmed.aan6205	journal	January 2018
pH-Sensitive Micelles Based on Star Copolymer Ad-(PCL-b-PDEAEMA-b-PPEGMA)4 for Controlled Drug Delivery Yang, Huiyan; Guo, Jianwei; Tong, Rui Polymers, Vol. 10, Issue 4 https://doi.org/10.3390/polym10040443	journal	April 2018
Overcoming the Limits of Flash Nanoprecipitation: Effective Loading of Hydrophilic Drug into Polymeric Nanoparticles with Controlled Structure Massella, Daniele; Celasco, Edvige; Salaün, Fabien Polymers, Vol. 10, Issue 10 https://doi.org/10.3390/polym10101092	journal	October 2018
pH-Responsive Micelles Assembled by Three-Armed Degradable Block Copolymers with a Cholic Acid Core for Drug Controlled-Release Feng, Jingjie; Wen, Weiqiu; Jia, Yong-Guang Polymers, Vol. 11, Issue 3 https://doi.org/10.3390/polym11030511	journal	March 2019

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