Cellular uptake and fate of cationic polymer-coated nanodiamonds delivering siRNA: a mechanistic study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00581897" target="_blank" >RIV/61388963:_____/24:00581897 - isvavai.cz</a>

Alternative codes found

RIV/61389005:_____/24:00581897 RIV/68378050:_____/24:00581897 RIV/00216208:11310/24:10494305

Result on the web

<a href="https://doi.org/10.1039/D3NR05738K" target="_blank" >https://doi.org/10.1039/D3NR05738K</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d3nr05738k" target="_blank" >10.1039/d3nr05738k</a>

Result language

angličtina

Original language name

Cellular uptake and fate of cationic polymer-coated nanodiamonds delivering siRNA: a mechanistic study

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

21001 - Nano-materials (production and properties)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nanoscale

ISSN

2040-3364

e-ISSN

2040-3372

Volume of the periodical

16

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

2490-2503

UT code for WoS article

001139131500001

EID of the result in the Scopus database

2-s2.0-85182375872