Diamond nanoparticles (nanodiamonds) can transport active drugs in cultured cells as well as in vivo. However, in the latter case, methods allowing the determination of their bioavailability accurately are still lacking. A nanodiamond can be made fluorescent with a perfectly stable emission and a lifetime ten times longer than that of tissue autofluorescence. Taking advantage of these properties, we present an automated quantification method of fluorescent nanodiamonds (FND) in histological sections of mouse organs and tumors, after systemic injection. We use a home-made time-delayed fluorescence microscope comprising a custom pulsed laser source synchronized on the master clock of a gated intensified array detector. This setup allows ultra-high-resolution images (120 Mpixels in size) of whole mouse organ sections to be obtained, with subcellular resolution and single-particle sensitivity. As a proof-of-principle experiment, we quantified the biodistribution and aggregation state of new cationic FNDs capable of transporting small interfering RNA inhibiting the oncogene responsible for Ewing sarcoma. Image analysis showed a low yield of nanodiamonds in the tumor after intravenous injection. Thus, for the in vivo efficacy assay, we injected the nanomedicine into the tumor. We achieved a 28-fold inhibition of the oncogene. This method can readily be applied to other nanoemitters with ≈100 ns lifetime.

Drug Delivery and Targeting Functional Validation and Preclinical Research 08035 Barcelona Spain

IMSTAR S A 75014 Paris France

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences 166 10 Prague Czech Republic

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences 166 10 Prague Czech Republic and Department of Chemical Engineering University of Chemistry and Technology 166 28 Prague Czech Republic

Sarcoma Research Group Oncobell Program CIBERONC Bellvitge Biomedical Research Institute 08908 L'Hospitalet de Llobregat Barcelona Spain

Université Paris Saclay ENS Paris Saclay CNRS CentraleSupélec LuMIn 91190 Gif sur Yvette France

Université Paris Saclay ENS Paris Saclay CNRS CentraleSupélec LuMIn 91190 Gif sur Yvette France and Université Paris Saclay Institut Gustave Roussy CNRS Metabolic and Systemic Aspects of Oncogenesis 94805 Villejuif France

Université Paris Saclay Institut d'Optique Graduate School CNRS Laboratoire Charles Fabry 91127 Palaiseau France

Université Paris Saclay Institut Gustave Roussy CNRS Metabolic and Systemic Aspects of Oncogenesis 94805 Villejuif France

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