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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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    SYSNO ASEP0542687
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleHarnessing subcellular-resolved organ distribution of cationic copolymer-functionalized fluorescent nanodiamonds for optimal delivery of active siRNA to a xenografted tumor in mice
    Author(s) Claveau, S. (FR)
    Kindermann, Marek (UOCHB-X)
    Papine, A. (FR)
    Díaz-Riascos, Z. V. (ES)
    Délen, X. (FR)
    Georges, P. (FR)
    López-Alemany, R. (ES)
    Tirado, O. M. (ES)
    Bertrand, J.-R. (FR)
    Abasolo, I. (ES)
    Cígler, Petr (UOCHB-X) RID, ORCID
    Treussart, F. (FR)
    Source TitleNanoscale - ISSN 2040-3364
    Roč. 13, č. 20 (2021), s. 9280-9292
    Number of pages12 s.
    Languageeng - English
    CountryGB - United Kingdom
    Keywordsprotein corona ; drug-delivery ; cells
    OECD categoryNano-materials (production and properties)
    R&D ProjectsGA18-17071S GA ČR - Czech Science Foundation (CSF)
    EF16_019/0000729 GA MŠk - Ministry of Education, Youth and Sports (MEYS)
    EF16_026/0008382 GA MŠk - Ministry of Education, Youth and Sports (MEYS)
    Research InfrastructureCANAM II - 90056 - Ústav jaderné fyziky AV ČR, v. v. i.
    Method of publishingLimited access
    Institutional supportUOCHB-X - RVO:61388963
    UT WOS000649764500001
    EID SCOPUS85106949710
    DOI10.1039/d1nr00146a
    AnnotationDiamond 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.
    WorkplaceInstitute of Organic Chemistry and Biochemistry
    Contactasep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
    Year of Publishing2022
    Electronic addresshttps://doi.org/10.1039/D1NR00146A
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