Carbosilane dendrimers with phosphonium terminal groups are low toxic non-viral transfection vectors for siRNA cell delivery.

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985858%3A_____%2F19%3A00512110" target="_blank" >RIV/67985858:_____/19:00512110 - isvavai.cz</a>

Alternative codes found

RIV/44555601:13440/19:43894626

Result on the web

<a href="http://hdl.handle.net/11104/0302316" target="_blank" >http://hdl.handle.net/11104/0302316</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijpharm.2019.03.018" target="_blank" >10.1016/j.ijpharm.2019.03.018</a>

Result language

angličtina

Original language name

Carbosilane dendrimers with phosphonium terminal groups are low toxic non-viral transfection vectors for siRNA cell delivery.

Original language description

Non-viral gene delivery vectors studied in the gene therapy applications are often designed with the cationic nitrogen containing groups necessary for binding and cell release of nucleic acids. Disadvantage is a relatively high toxicity which restricts the in vivo use of such nanoparticles. Here we show, that the 3rd generation carbosilane dendrimers possessing (trimethyl)phosphonium (PMe 3 ) groups on their periphery were able to effectively deliver the functional siRNA into the cells (B14, Cricetulus griseus), release it into the cytosol and finally to achieve up to 40% gene silencing of targeted gene (glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) with the comparable or, in some cases, even better effectivity as their ammonium counterparts. Moreover, such cationic dendrimers show relatively low in vivo toxicity as compared to their ammonium analogues when analyzed by standard fish embryo test (FET) on Danio rerio in vivo model, with LD 50 = 6.26 µM after 48 h of incubation. This is more than 10-fold improvement as compared to published values for various other types of cationic dendrimers. We discuss the potential of further increase of the transfection efficiency, endosomal escape and decrease of toxicity of such non-viral vectors, based on the systematic screening of different types of substituents on central phosphonium atom.

Czech name

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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

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OECD FORD branch

10401 - Organic chemistry

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

2019

Confidentiality

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

Name of the periodical

International Journal of Pharmaceutics

ISSN

0378-5173

e-ISSN

—

Volume of the periodical

652

Issue of the periodical within the volume

MAY 1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

51-65

UT code for WoS article

000463865000006

EID of the result in the Scopus database

2-s2.0-85063000514