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Harnessing subcellular-resolved organ distribution of cationic copolymer-functionalized fluorescent nanodiamonds for optimal delivery of active siRNA to a xenografted tumor in mice

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    0542687 - ÚOCHB 2022 RIV GB eng J - Journal Article
    Claveau, S. - Kindermann, Marek - Papine, A. - Díaz-Riascos, Z. V. - Délen, X. - Georges, P. - López-Alemany, R. - Tirado, O. M. - Bertrand, J.-R. - Abasolo, I. - Cígler, Petr - Treussart, F.
    Harnessing subcellular-resolved organ distribution of cationic copolymer-functionalized fluorescent nanodiamonds for optimal delivery of active siRNA to a xenografted tumor in mice.
    Nanoscale. Roč. 13, č. 20 (2021), s. 9280-9292. ISSN 2040-3364. E-ISSN 2040-3372
    R&D Projects: GA ČR(CZ) GA18-17071S; GA MŠk(CZ) EF16_019/0000729; GA MŠk(CZ) EF16_026/0008382
    Research Infrastructure: CANAM II - 90056
    Institutional support: RVO:61388963
    Keywords : protein corona * drug-delivery * cells
    OBOR OECD: Nano-materials (production and properties)
    Impact factor: 7.790, year: 2020
    https://doi.org/10.1039/D1NR00146A

    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.
    Permanent Link: http://hdl.handle.net/11104/0320065
     
     
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