Article

Journal of Materials Science: Materials in Medicine

, Volume 23, Issue 10, pp 2399-2412

In vitro and in vivo investigations of upconversion and NIR emitting Gd2O3:Er3+,Yb3+ nanostructures for biomedical applications

  • Eva HemmerAffiliated withCenter for Technologies Against Cancer (CTC), Tokyo University of Science Email author 
  • , Hiroyuki TakeshitaAffiliated withDivision of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science
  • , Tomoyoshi YamanoAffiliated withDivision of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science
  • , Takanori FujikiAffiliated withDepartment of Materials Science and Technology, Tokyo University of Science
  • , Yvonne KohlAffiliated withDepartment of Cell Biology & Applied Virology, Fraunhofer Institute for Biomedical Engineering
  • , Karin LöwAffiliated withDepartment of Cell Biology & Applied Virology, Fraunhofer Institute for Biomedical Engineering
  • , Nallusamy VenkatachalamAffiliated withDepartment of Materials Science and Technology, Tokyo University of Science
  • , Hiroshi HyodoAffiliated withCenter for Technologies Against Cancer (CTC), Tokyo University of ScienceDepartment of Materials Science and Technology, Tokyo University of Science
  • , Hidehiro KishimotoAffiliated withCenter for Technologies Against Cancer (CTC), Tokyo University of ScienceDivision of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science
    • , Kohei SogaAffiliated withCenter for Technologies Against Cancer (CTC), Tokyo University of ScienceDepartment of Materials Science and Technology, Tokyo University of Science

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Abstract

The use of an “over 1000-nm near-infrared (NIR) in vivo fluorescence bioimaging” system based on lanthanide containing inorganic nanostructures emitting in the visible and NIR range under 980-nm excitation is proposed. It may overcome problems of currently used biomarkers including color fading, phototoxicity and scattering. Gd2O3:Er3+,Yb3+ nanoparticles and nanorods showing upconversion and NIR emission are synthesized and their cytotoxic behavior is investigated by incubation with B-cell hybridomas and macrophages. Surface modification with PEG-b-PAAc provides the necessary chemical durability reducing the release of toxic Gd3+ ions. NIR fluorescence microscopy is used to investigate the suitability of the nanostructures as NIR–NIR biomarkers. The in vitro uptake of bare and modified nanostructures by macrophages is investigated by confocal laser scanning microscopy. In vivo investigations revealed nanostructures in liver, lung, kidneys and spleen a few hours after injection into mice, while most of the nanostructures have been removed from the body after 24 h.