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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 ASEP 0542687 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Harnessing 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) ORCID
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 Title Nanoscale. - : Royal Society of Chemistry - ISSN 2040-3364
Roč. 13, č. 20 (2021), s. 9280-9292Number of pages 12 s. Language eng - English Country GB - United Kingdom Keywords protein corona ; drug-delivery ; cells OECD category Nano-materials (production and properties) R&D Projects GA18-17071S GA ČR - Czech Science Foundation (CSF) EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_026/0008382 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure CANAM II - 90056 - Ústav jaderné fyziky AV ČR, v. v. i. Method of publishing Limited access Institutional support UOCHB-X - RVO:61388963 UT WOS 000649764500001 EID SCOPUS 85106949710 DOI https://doi.org/10.1039/d1nr00146a Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2022 Electronic address https://doi.org/10.1039/D1NR00146A
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