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Phosphonium Carbosilane Dendrimers for Biomedical Applications – Synthesis, Characterization and Cytotoxicity Evaluation.

SYSNO ASEP	0473749
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Phosphonium Carbosilane Dendrimers for Biomedical Applications – Synthesis, Characterization and Cytotoxicity Evaluation.
Author(s)	Strašák, Tomáš (UCHP-M)_{RID, ORCID, SAI} Malý, J. (CZ) Wróbel, D. (CZ) Malý, M. (CZ) Herma, R. (CZ) Čermák, Jan (UCHP-M)_{RID, ORCID, SAI} Müllerová, Monika (UCHP-M)_{RID, ORCID, SAI} Červenková Šťastná, Lucie (UCHP-M)_{RID, ORCID, SAI} Cuřínová, Petra (UCHP-M)_{RID, SAI, ORCID}
Source Title	RSC Advances. - : Royal Society of Chemistry Roč. 7, č. 30 (2017), s. 18724-18744
Number of pages	21 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	modified ppi pendrimers ; molecular-dynamics ; gene delivery
Subject RIV	CC - Organic Chemistry
OECD category	Organic chemistry
Institutional support	UCHP-M - RVO:67985858
UT WOS	000399005500067
EID SCOPUS	85016408382
DOI	10.1039/c7ra01845b
Annotation	We report the synthesis and cytotoxicity evaluation of a completely new class of cationic carbosilane dendrimers functionalized with several different phosphonium peripheral groups and an ammonium functionalised one as a reference. The carbosilane dendrimers with NMe3, PMe3, P(Et2)2(CH2)3OH, PBu3, P(C6H4-OMe)3 and P(Ph)3 peripheral substituents were synthesized, thoroughly characterized and modelled by computer simulations. The cytotoxicities of the dendrimers were investigated in vitro on three model cell lines (B14, BRL and NRK cells) by MTT and CV assay methods. Generally, the cytotoxicities of PMe3 carbosilane dendrimers were similar or slightly lower when compared with NMe3 dendrimers. The substitution of methyl groups in PMe3 carbosilane dendrimers with more hydrophobic and bulky alkyl substituents (PBu3 and P(Et2)2(CH2)3OH dendrimers) resulted in an increase of cytotoxicity. The P(C6H4-OMe)3 dendrimer showed exceptionally low cytotoxicity across all cell lines or assay methods used. Generally, phosphonium carbosilane dendrimers could represent a valuable alternative to ammonium ones in gene therapy applications due to comparable or lower cytotoxicities, the presence of positive charge for nucleic acid electrostatic binding and in the cases of P(C6H4-OMe)3 and P(Ph)3 dendrimers high potential of mitochondrial targeting.
Workplace	Institute of Chemical Process Fundamentals
Contact	Eva Jirsová, jirsova@icpf.cas.cz, Tel.: 220 390 227
Year of Publishing	2018

Number of the records: 1