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

0473749 - ÚCHP 2018 RIV GB eng J - Článek v odborném periodiku
Strašák, Tomáš - Malý, J. - Wróbel, D. - Malý, M. - Herma, R. - Čermák, Jan - Müllerová, Monika - Červenková Šťastná, Lucie - Cuřínová, Petra
Phosphonium Carbosilane Dendrimers for Biomedical Applications – Synthesis, Characterization and Cytotoxicity Evaluation.
RSC Advances. Roč. 7, č. 30 (2017), s. 18724-18744. E-ISSN 2046-2069
Institucionální podpora: RVO:67985858
Klíčová slova: modified ppi pendrimers * molecular-dynamics * gene delivery
Obor OECD: Organic chemistry
Impakt faktor: 2.936, rok: 2017

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.
Trvalý link: http://hdl.handle.net/11104/0270991