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ACS Nano. 2016 May 24;10(5):5468-78. doi: 10.1021/acsnano.6b01879. Epub 2016 Apr 28.

Three-Dimensional Optical Mapping of Nanoparticle Distribution in Intact Tissues.

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Institute of Biomaterials and Biomedical Engineering, University of Toronto , Rosebrugh Building, Room 407, 164 College Street, Toronto, Ontario M5S 3G9, Canada.
Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
Discovery Oncology, Pharmaceutical Research and Early Development, Roche Innovation Center Munich , Nonnenwald 2, 82377 Penzberg, Germany.
Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto , 160 College Street, Room 230, Toronto, Ontario M5S 3E1, Canada.
Department of Chemical Engineering, University of Toronto , 200 College Street, Toronto, Ontario M5S 3E5, Canada.
Department of Material Science and Engineering, University of Toronto , 184 College Street, Suite 140, Toronto, Ontario M5S 3E1, Canada.


The role of tissue architecture in mediating nanoparticle transport, targeting, and biological effects is unknown due to the lack of tools for imaging nanomaterials in whole organs. Here, we developed a rapid optical mapping technique to image nanomaterials in intact organs ex vivo and in three-dimensions (3D). We engineered a high-throughput electrophoretic flow device to simultaneously transform up to 48 tissues into optically transparent structures, allowing subcellular imaging of nanomaterials more than 1 mm deep into tissues which is 25-fold greater than current techniques. A key finding is that nanomaterials can be retained in the processed tissue by chemical cross-linking of surface adsorbed serum proteins to the tissue matrix, which enables nanomaterials to be imaged with respect to cells, blood vessels, and other structures. We developed a computational algorithm to analyze and quantitatively map nanomaterial distribution. This method can be universally applied to visualize the distribution and interactions of materials in whole tissues and animals including such applications as the imaging of nanomaterials, tissue engineered constructs, and biosensors within their intact biological environment.


3D imaging; CLARITY; microscopy; nanoparticle biological interactions; nanoparticles; nanosystems; nanotoxicology; nano−bio interface; optical clearing; protein corona; whole organ distribution

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