Swarming behavior and in vivo monitoring of enzymatic nanomotors within the bladder.

Journal: Science robotics
PMID:

Abstract

Enzyme-powered nanomotors are an exciting technology for biomedical applications due to their ability to navigate within biological environments using endogenous fuels. However, limited studies into their collective behavior and demonstrations of tracking enzyme nanomotors in vivo have hindered progress toward their clinical translation. Here, we report the swarming behavior of urease-powered nanomotors and its tracking using positron emission tomography (PET), both in vitro and in vivo. For that, mesoporous silica nanoparticles containing urease enzymes and gold nanoparticles were used as nanomotors. To image them, nanomotors were radiolabeled with either I on gold nanoparticles or F-labeled prosthetic group to urease. In vitro experiments showed enhanced fluid mixing and collective migration of nanomotors, demonstrating higher capability to swim across complex paths inside microfabricated phantoms, compared with inactive nanomotors. In vivo intravenous administration in mice confirmed their biocompatibility at the administered dose and the suitability of PET to quantitatively track nanomotors in vivo. Furthermore, nanomotors were administered directly into the bladder of mice by intravesical injection. When injected with the fuel, urea, a homogeneous distribution was observed even after the entrance of fresh urine. By contrast, control experiments using nonmotile nanomotors (i.e., without fuel or without urease) resulted in sustained phase separation, indicating that the nanomotors' self-propulsion promotes convection and mixing in living reservoirs. Active collective dynamics, together with the medical imaging tracking, constitute a key milestone and a step forward in the field of biomedical nanorobotics, paving the way toward their use in theranostic applications.

Authors

  • Ana C Hortelao
    Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10-12, 08028 Barcelona Spain.
  • Cristina Simó
    CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Guipúzcoa, Spain.
  • Maria Guix
    Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10-12, 08028 Barcelona Spain.
  • Sandra Guallar-Garrido
    Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
  • Esther Julián
    Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
  • Diana Vilela
    Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10-12, 08028 Barcelona Spain.
  • Luka Rejc
    CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Guipúzcoa, Spain.
  • Pedro Ramos-Cabrer
    CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Guipúzcoa, Spain.
  • Unai Cossío
    CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Guipúzcoa, Spain.
  • Vanessa Gómez-Vallejo
    CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Guipúzcoa, Spain.
  • Tania Patiño
    Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Jordi Llop
    CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Guipúzcoa, Spain. jllop@cicbiomagune.es ssanchez@ibecbarcelona.eu.
  • Samuel Sanchez