Phosphonium carbosilane dendrimers for biomedical applications – synthesis, characterization and cytotoxicity evaluation

Strašák, Tomáš; Malý, Jan; Wrobel, Dominika; Malý, Marek; Herma, Regina; Čermák, Jan; Müllerová, Monika; Šťastná, Lucie Červenková; Cuřínová, Petra

doi:10.1039/c7ra01845b

Cited by 23 publications

(29 citation statements)

References 64 publications

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“…For this study, the dendrimers previously prepared in our group were used. Several batches of each dendrimer type differing by purity were usually obtained in the course of the synthetic sequence optimization.…”

Section: Methodsmentioning

confidence: 99%

“…1D NMR spectra of all studied dendrimers were reported previously . The structures of products and the peak assignment were confirmed by gCOSY.…”

Section: Methodsmentioning

confidence: 99%

“…To obtain dendrimers with similar hydrophobic/hydrophilic core‐shell structure but lower toxicity, we decided to substitute QAS at the periphery for commonly more biocompatible phosphonium groups. A series of polyphosphonium carbosilane dendrimers was prepared, and their cytotoxicity was tested in vitro …”

Section: Introductionmentioning

confidence: 99%

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ESI‐TOF mass spectrometry of cationic carbosilane dendrimers: A potent tool for characterization of structural defects

et al. 2018

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Macromolecular polyelectrolytes are gaining considerable attention for the application in medicine that implies their detailed characterization. We have successfully applied electrospray ionization mass spectrometry (ESI MS) to the analysis of defects in the structure of three generations of polycationic carbosilane dendrimers bearing series of quarternary phosphonium groups at their periphery. Besides expected defects caused by incomplete conversion of particular reaction steps during the synthesis of dendritic scaffold and subsequent peripheral functionalization, also, several products of side reactions were observed together with defects created in the course of measurement (particularly ion exchange products). Defective molecules can be to some extent separated by means of gel permeation chromatography that proves that they are not products of in source fragmentation processes. Within the reaction sequence used for the synthesis of dendrimers under study, hydrosilylation was the source of most defects; the effectivity of quarternization depends on the type of phosphine. Results confirm high sensitivity of ESI MS towards defects, stability of the carbosilane skeleton towards fragmentation under the conditions of ESI ionization, and capability to detect both lower- and higher-molecular weight impurities arising from the synthetic sequence in the same m/z range as the target dendrimer, thus providing valuable view of the polydispersity.

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Section: Methodsmentioning

confidence: 99%

“…1D NMR spectra of all studied dendrimers were reported previously . The structures of products and the peak assignment were confirmed by gCOSY.…”

Section: Methodsmentioning

confidence: 99%

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ESI‐TOF mass spectrometry of cationic carbosilane dendrimers: A potent tool for characterization of structural defects

et al. 2018

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“…As reported in Table , all the amphiphilic compounds only marginally affected cell growth, since viability values were in the range 79.9–111.7% for B14 cells and 79.6–105.8% for BRL cells, and, even if not extravagantly, they were less cytotoxic than dendrimers H1 and H2 not equipped with the C‐18 chain. Furthermore the achieved amphiphilic dendrimers were found to be much less cytotoxic than PEI25K that at a concentration of 40 µg mL −1 determines the survival of only 30–40% of two cancer cell lines …”

Section: Resultsmentioning

confidence: 99%

Synthesis and characterization of versatile amphiphilic dendrimers peripherally decorated with positively charged amino acids

Alfei

Catena

2018

Polymer International

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Dendrimers are nanostructured ‘architectural motifs’ with a well‐tailored polymeric structure, symmetric tree‐like shape and the presence of several functional groups and inner cavities, and are of eminent interest in many biomedical applications such as drug delivery, gene transfection and imaging. In the work reported, reliable protocols for the synthesis of polyester‐based, hydrolysable, amphiphilic polycationic dendrimers were developed. A C‐18 hydrocarbon chain provided by a biocompatible fatty acid, stearic acid, and second‐ and third‐generation dendrons based on 2,2‐bis(hydroxymethyl)propionic acid were built on 2,2‐bis(hydroxymethyl)propanol and pentaerythritol as core molecules. αN‐BOC‐ω'N‐(NO2)‐l‐arginine alone, mixed with αN,ϵN‐di‐BOC‐l‐lysine or also with N,N′‐dimethylglycine and αN‐BOC‐methylglycine were successfully bound to the prepared polyester neutral scaffolds and, after the removal of protecting groups, five cationic dendrimers were obtained. Their structure was confirmed using NMR analysis and experimental molecular weight. Their buffer capacity, comparable to that of polyethyleneimines, was optimal, high viability percentage values were obtained from cytotoxicity assays and zeta potential and mean particle size were in the desired ranges. The synthesized nanostructured compounds that harmonize a multifunctional polycationic shell, a biodegradable uncharged polyester matrix and a C‐18 hydrophobic portion helpful for an improved hydrophilic–lipophilic balance in their structure embody all the fundamental features to be suitable for biomedical applications. © 2018 Society of Chemical Industry

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“…(Rose et al, ) Phosphonium containing compounds are generally less toxic than their ammonium equivalents due to differences in ionic radius and charge distribution. (Rose et al, ; Stekar et al, ; Strasak et al, ) In addition, phosphonium based lipids have been shown to transfect cells with high efficacies and lower toxicity than ammonium analogues. (Guenin et al, ) Interestingly, the few polymeric phosphonium materials reported so far in the literature showed a similar trend in relation to toxicity.…”

Section: Introductionmentioning

confidence: 99%

Branched poly (trimethylphosphonium ethylacrylate‐co‐PEGA) by RAFT: alternative to cationic polyammoniums for nucleic acid complexation

Cook

Peltier

Barlow

et al. 2018

J of Interdiscip Nanomed

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Cationic and highly branched poly (trimethylphosphonium ethylacrylate‐co‐poly (ethylene glycol) acrylate) (p (TMPEA‐co‐PEGA)), and its ammonium equivalent, have been synthesised from post‐polymerisation modification of a poly (bromo ethylacrylate‐co‐poly (ethylene glycol) acrylate) (p (BEA‐co‐PEGA)) precursor polymer produced using reversible addition fragmentation chain transfer (RAFT) polymerisation. The cationic polymers were evaluated for their ability to complex nucleic acids, their in vitro cytotoxicity and their GFP pDNA transfection efficiency. The results show RAFT copolymerisation of BEA and PEGA is a simple route to polyphosphoniums showing reduced cytotoxicities and higher transfection efficiencies than their polyammonium alternatives.

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Phosphonium carbosilane dendrimers for biomedical applications – synthesis, characterization and cytotoxicity evaluation

Abstract: Phosphonium carbosilane dendrimers could represent an alternative to ammonium ones in gene therapy applications with high potential of mitochondrial targeting.

Cited by 23 publications

References 64 publications

ESI‐TOF mass spectrometry of cationic carbosilane dendrimers: A potent tool for characterization of structural defects

ESI‐TOF mass spectrometry of cationic carbosilane dendrimers: A potent tool for characterization of structural defects

Synthesis and characterization of versatile amphiphilic dendrimers peripherally decorated with positively charged amino acids

Branched poly (trimethylphosphonium ethylacrylate‐co‐PEGA) by RAFT: alternative to cationic polyammoniums for nucleic acid complexation

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