title: Analyzing spatiotemporal distribution of uniquely fluorescent nanoparticles in xenograft tumors.
abstract: A dose circulating through the blood at one time will have different opportunities to access the tumor compared to a dose circulating hours later. Methods to test this hypothesis allowed us to differentiate two uniquely fluorescent doses of nanoparticles (administered as a mixture or sequentially) and to measure the distribution and correlation of these nanoparticle doses in three dimensions. Multiple colocalization analyses confirm that silica nanoparticles separated into different dose administrations will not accumulate in the same location. Decreased colocalization between separate doses implies dynamic extravasation events on the scale of microns. Further, the perfusion state of different blood vessels can change across the dosing period. Lastly, analyzing the distance traveled by these silica nanoparticles in two dimensions can be an overestimation when compared with three-dimensional distance analysis. Better understanding intratumoral distribution of delivered drugs will be crucial to overcoming the various barriers to transport in solid tumors.
authors.affiliation: Department of Bioengineering, The University of Utah, United States.
authors.forename: Darren L
authors.initials: DL
authors.lastname: Stirland
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan; Department of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Toh
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, United States; Utah-Inha DDS and Advanced Therapeutics Research Center, Incheon, Republic of Korea. Electronic address: you.bae@utah.edu.
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000032:analysis* / Q000378:metabolism; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000032:analysis* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D012822:Silicon Dioxide / Q000032:analysis* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D012822:Silicon Dioxide
keywords: Dynamic drug delivery; Extravasation; Nanoparticles; Perfusion; Solid tumors