The consideration of human and environmental exposure to dendrimers, including cytotoxicity, acute toxicity, and cell and tissue accumulation, is essential due to their significant potential for various biomedical applications. This study aimed to evaluate the biodistribution and toxicity of a novel methoxyphenyl phosphonium carbosilane dendrimer, a potential mitochondria-targeting vector for cancer therapeutics, in 2D and 3D cancer cell cultures and zebrafish embryos. We assessed its cytotoxicity (via MTT, ATP, and Spheroid growth inhibition assays) and cellular biodistribution. The dendrimer cytotoxicity was higher in cancer cells, likely due to its specific targeting to the mitochondrial compartment. In vivo studies using zebrafish demonstrated dendrimer distribution within the vascular and gastrointestinal systems, indicating a biodistribution profile that may be beneficial for systemic therapeutic delivery strategies. The methoxyphenyl phosphonium carbosilane dendrimer shows promise for applications in cancer cell delivery, but additional studies are required to confirm these findings using alternative labelling methods and more physiologically relevant models. Our results contribute to the growing body of evidence supporting the potential of carbosilane dendrimers as vectors for cancer therapeutics.
- MeSH
- dánio pruhované MeSH
- dendrimery * toxicita MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- techniky 3D buněčné kultury MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Průmyslové kultivace jsou klíčovým zdroje mnoha produktů. Každá kultivace má své vlastní produkční kmeny, podmínky a apara‐ tury. Nejčastěji používané jsou mechanicky míchané bioreaktory, díky jejich efektivní homogenizaci a všestrannosti. Přesto nejsou kompletně kompatibilní s organismy citlivými na střižné síly. Pro kultivaci takových organismů je vhodnější probublávaná kolona. Obecné porovnání probublávané kolony s míchaným bioreaktorem je náročné, jelikož je každá kultivace specifická. Probublávané kolony jsou jednoduché a snadno konstruovatelné bioreaktory, které vyžadují menší počáteční kapitál v porovnání s mechanicky míchaným bioreaktorem. Probublávané kolony nemají vnitřní komponenty a složité mechanické části a jsou proto méně náročné na údržbu. Nicméně, nejsou tak všestranné jako míchané bioreaktory a jsou mnohem více účelově používané. Přesto jsou v dnešním průmyslu nenahraditelné, především při velkoobjemových kultivacích mechanicky citlivých buněk, jako produkce kyseliny citrónové nebo antibiotik. Přímé porovnání probublávané kolony s mechanicky míchaným bioreaktorem je složité. Existují studie zaměřené na porovnání těch‐ to bioreaktorů při specifických kultivacích. Volba mezi těmito bioreaktory přesto závisí na dané aplikaci, buněčné linii a ekonomice celého procesu.
Industrial cultivations are a key source of many products. Each cultivation requires a specific producing organism, conditions and apparatus. Stirred tanks are most commonly used bioreactors, due to their efficient homogenization and versatility. However, they are not entirely suitable for cultivation of shear sensitive cells. Bubble columns are more suitable option for shear sensitive cells. Overall comparison of bubble columns and stirred tanks is complicated, since every cultivation is situational. Bubble columns are simple and easy to build bioreactors, which require a smaller starting investment compared to STRs. In the case of BCs without the internals, they required less maintenance due to lack of complex mechanical parts. However, BCs are not as ver‐ satile as STRs and are much more situational. Even though, they are unreplaceable part of today’s industry, especially in cultivations of shear sensitive cells in high volumes, like production of citric acid or antibiotics. Direct comparison of BC and STR is difficult. Some studies have conducted tests with specific cultivations on minds. Still, the final choice between these bioreactors depends on application, cell line used and final economics of the entire process.
Nanoscale titanium dioxide (nanoTiO2) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO2 is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO2. This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C6-C12) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 × 10(4) to 2.32 × 10(4) particles/cm(3) with ∼80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m(3). All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p < 0.001). A significant dose-dependent association was found between exposure to TiO2 and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO2 complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles.
- MeSH
- biologické markery analýza moč MeSH
- chemický průmysl MeSH
- dechové testy MeSH
- dinoprost analogy a deriváty analýza moč MeSH
- lidé MeSH
- malondialdehyd analýza moč MeSH
- metabolismus lipidů MeSH
- monitorování životního prostředí metody MeSH
- nanočástice analýza toxicita MeSH
- oxidace-redukce MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- poškození DNA MeSH
- pracovní expozice škodlivé účinky analýza MeSH
- spektrofotometrie atomová MeSH
- titan analýza toxicita MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
