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Cellular uptake and fate of cationic polymer-coated nanodiamonds delivering siRNA: a mechanistic study
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SYSNO ASEP 0581897 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Cellular uptake and fate of cationic polymer-coated nanodiamonds delivering siRNA: a mechanistic study Tvůrce(i) Majer, Jan (UOCHB-X)
Kindermann, Marek (UOCHB-X)
Pinkas, Dominik (UMG-J) ORCID
Chvátil, David (UJF-V) RID, SAI, ORCID
Cígler, Petr (UOCHB-X) RID, ORCID
Libusová, L. (CZ)Zdroj.dok. Nanoscale. - : Royal Society of Chemistry - ISSN 2040-3364
Roč. 16, č. 5 (2024), s. 2490-2503Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova lysine-functionalized nanodiamonds ; fluorescent nanodiamonds ; nanoparticles CEP EF16_026/0008382 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Výzkumná infrastruktura Czech-BioImaging II - 90129 - Ústav molekulární genetiky AV ČR, v. v. i.
Czech-BioImaging III - 90250 - Ústav molekulární genetiky AV ČR, v. v. i.Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 ; UMG-J - RVO:68378050 ; UJF-V - RVO:61389005 UT WOS 001139131500001 EID SCOPUS 85182375872 DOI 10.1039/d3nr05738k Anotace Gene silencing using small interfering RNAs (siRNAs) is a selective and promising approach for treatment of numerous diseases. However, broad applications of siRNAs are compromised by their low stability in a biological environment and limited ability to penetrate cells. Nanodiamonds (NDs) coated with cationic polymers can enable cellular delivery of siRNAs. Recently, we developed a new type of ND coating based on a random copolymer consisting of (2-dimethylaminoethyl) methacrylate (DMAEMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) monomers. These hybrid ND-polymer particles (Cop+-FND) provide near-infrared fluorescence, form stable complexes with siRNA in serum, show low toxicity, and effectively deliver siRNA into cells in vitro and in vivo. Here, we present data on the mechanism of cellular uptake and cell trafficking of Cop+-FND : siRNA complexes and their ability to selectively suppress mRNA levels, as well as their cytotoxicity, viability and colloidal stability. We identified clathrin-mediated endocytosis as the predominant entry mechanism for Cop+-FND : siRNA into U-2 OS human bone osteosarcoma cells, with a substantial fraction of Cop+-FND : siRNA following the lysosome pathway. Cop+-FND : siRNA potently inhibited the target GAPDH gene with negligible toxicity and sufficient colloidal stability. Based on our results, we suggest that Cop+-FND : siRNA can serve as a suitable in vivo delivery system for siRNA. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2025 Elektronická adresa https://doi.org/10.1039/D3NR05738K
Počet záznamů: 1