PT  - JOURNAL ARTICLE
AU  - Ana C. Hortelao
AU  - Cristina Simó
AU  - Maria Guix
AU  - Sandra Guallar-Garrido
AU  - Esther Julián
AU  - Diana Vilela
AU  - Luka Rejc
AU  - Pedro Ramos-Cabrer
AU  - Unai Cossío
AU  - Vanessa Gómez-Vallejo
AU  - Tania Patiño
AU  - Jordi Llop
AU  - Samuel Sánchez
TI  - Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT
AID  - 10.1101/2020.06.22.146282
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.22.146282
4099  - http://biorxiv.org/content/early/2020/06/23/2020.06.22.146282.short
4100  - http://biorxiv.org/content/early/2020/06/23/2020.06.22.146282.full
AB  - Enzyme powered nanomotors hold great potential for biomedical applications, as they show improved diffusion and navigation within biological environments using endogenous fuels. Yet, understanding their collective behavior and tracking them in vivo is paramount for their clinical translation. Here, we report on the in vitro and in vivo study of swarms of self-propelled enzyme-nanomotors and the effect of collective behavior on the nanomotors distribution within the bladder. For that purpose, mesoporous silica nanomotors were functionalized with urease enzymes and gold nanoparticles. Two radiolabeling strategies, i.e. absorption of 124I on gold nanoparticles and covalent attachment of an 18F-labeled prosthetic group to urease, were assayed. In vitro experiments using optical microscopy and positron emission tomography (PET) showed enhanced fluid mixing and collective migration of nanomotors in phantoms containing complex paths. Biodistribution studies after intravenous administration in mice confirmed the biocompatibility of the nanomotors at the administered dose, the suitability of PET to quantitatively track nanomotors in vivo, and the convenience of the 18F-labeling strategy. Furthermore, intravesical instillation of nanomotors within the bladder in the presence of urea resulted in a homogenous distribution after the entrance of fresh urine. Control experiments using BSA-coated nanoparticles or nanomotors in water resulted in sustained phase separation inside the bladder, demonstrating that the catalytic decomposition of urea can provide urease-nanomotors with active motion, convection and mixing capabilities in living reservoirs. This active collective dynamics, together with the medical imaging tracking, constitutes a key milestone and a step forward in the field of biomedical nanorobotics, paving the way towards their use in theranostic applications.Competing Interest StatementThe authors have declared no competing interest.