title: Tailoring nanoparticle designs to target cancer based on tumor pathophysiology.
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.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9;
authors.forename: Edward A
authors.initials: EA
authors.lastname: Sykes
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9;
authors.forename: Qin
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Biomedical Engineering, University of Calgary, Calgary, AB, Canada T2N 1N4;
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Sarsons
authors.affiliation: Department of Medical Biophysics, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada M5G 1L7;
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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;
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Rocheleau
authors.affiliation: Department of Pathology, University Health Network, Toronto, ON, Canada M5G 2C4;
authors.forename: David M
authors.initials: DM
authors.lastname: Hwang
authors.affiliation: Department of Medical Biophysics, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada M5G 1L7;
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Chemistry, University of Calgary, Calgary, AB, Canada T2N 1N4;
authors.forename: David T
authors.initials: DT
authors.lastname: Cramb
authors.affiliation: Biomedical Engineering, University of Calgary, Calgary, AB, Canada T2N 1N4;
authors.forename: Kristina D
authors.initials: KD
authors.lastname: Rinker
authors.affiliation: 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.
authors.forename: Warren C W
authors.initials: WC
authors.lastname: Chan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D045744:Cell Line, Tumor; D005260:Female; D006046:Gold / Q000737:chemistry; D064593:Heterografts; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D008819:Mice, Nude; D009010:Monte Carlo Method; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D006046:Gold
keywords: cancer; nanoparticles; nano–bio interactions; targeting; tumor