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Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1142-51. doi: 10.1073/pnas.1521265113. Epub 2016 Feb 16.

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology.

Author information

1
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9;
2
Biomedical Engineering, University of Calgary, Calgary, AB, Canada T2N 1N4;
3
Department of Medical Biophysics, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada M5G 1L7;
4
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9; Toronto General Research Institute, University Health Network, Toronto, ON, Canada M5G 2M9;
5
Department of Pathology, University Health Network, Toronto, ON, Canada M5G 2C4;
6
Department of Chemistry, University of Calgary, Calgary, AB, Canada T2N 1N4;
7
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9; Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3E1; Department of Chemistry, University of Toronto, ON, Canada M5S 3H6; Department of Chemical Engineering, University of Toronto, ON, Canada M5S 3E5; Department of Materials Science and Engineering, University of Toronto, ON, Canada M5S 3E4 warren.chan@utoronto.ca.

Abstract

Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient's disease state to achieve optimal diagnostic and therapeutic outcomes.

KEYWORDS:

cancer; nanoparticles; nano–bio interactions; targeting; tumor

PMID:
26884153
PMCID:
PMC4780626
DOI:
10.1073/pnas.1521265113
[Indexed for MEDLINE]
Free PMC Article

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