The molecular weight (Mw) of dextran derivatives, such as regioselectively oxidized dicarboxydextran (DXA), is greatly influencing their faith in an organism, which could be possibly used to improve anticancer drug delivery. Here we present a modified method of sulfonation-induced chain scission allowing direct and accurate control over the Mw of DXA without increasing its polydispersity. Prepared DXA derivatives (Mw = 10-185 kDa) have been conjugated to cisplatin and the Mw of the carrier found to have a significant impact on cisplatin release rates, in vitro cytotoxicity, and migrastatic potential. Conjugates with the high-Mw DXA showed particularly increased anticancer efficacy. The best conjugate was four times more effective against malignant prostatic cell lines than free cisplatin and significantly inhibited the ovarian cancer cell migration. This was traced to the characteristics of spontaneously formed cisplatin-crosslinked DXA nanogels influenced by Mw of DXA and amount of loaded cisplatin.
- Klíčová slova
- Carrier, Cisplatin, Dextran, Drug-delivery, Molecular weight, Periodate oxidation,
- MeSH
- adenokarcinom farmakoterapie metabolismus MeSH
- antitumorózní látky chemie farmakologie MeSH
- buňky A549 MeSH
- cisplatina chemie farmakologie MeSH
- dextrany chemie MeSH
- lidé MeSH
- molekulová hmotnost MeSH
- nádory prostaty farmakoterapie metabolismus MeSH
- nádory vaječníků farmakoterapie metabolismus MeSH
- nádory farmakoterapie metabolismus MeSH
- nanogely chemie MeSH
- nosiče léků chemie MeSH
- oxidace-redukce MeSH
- pohyb buněk účinky léků MeSH
- systémy cílené aplikace léků metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky MeSH
- cisplatina MeSH
- dextrany MeSH
- nanogely MeSH
- nosiče léků MeSH
Increased oxidative stress is indisputably an important mechanism of doxorubicin side effects, especially its cardiotoxicity. To prevent impairment of non-tumorous tissue and to improve the specificity in targeting the tumor tissue, new drug nanotransporters are developed. In many cases preclinical therapeutic advantage has been shown when compared with the administration of conventional drug solution. Three forms of doxorubicin--conventional (DOX), encapsulated in liposomes (lipoDOX) and in apoferritin (apoDOX) were applied to Wistar rats. After 24 h exposition, the plasma level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipoperoxidation and tissue gene expression of thioredoxin reductase 2 (TXNRD2) and aldehyde dehydrogenase 3A1 (ALDH3A1) as an important part of antioxidative system were determined. Only conventional DOX significantly increases the level of 4-HNE; encapsulated forms on the other hand show significant decrease in plasma levels of 4-HNE in comparison with DOX. They also cause significant decrease in gene expression of ALDH3A1 and TXNRD2 in liver as a main detoxification organ, and a mild influence on the expression of these enzymes in left heart ventricle as a potential target of toxicity. Thus, 4-HNE seems to be a good potential biomarker of oxidative stress induced by various forms of doxorubicin.
- MeSH
- aldehyddehydrogenasa genetika metabolismus MeSH
- aldehydy krev MeSH
- antibiotika antitumorózní aplikace a dávkování chemie toxicita MeSH
- apoferritiny aplikace a dávkování chemie toxicita MeSH
- biologické markery krev MeSH
- chemie farmaceutická MeSH
- down regulace MeSH
- doxorubicin aplikace a dávkování analogy a deriváty chemie toxicita MeSH
- játra účinky léků enzymologie MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- polyethylenglykoly aplikace a dávkování chemie toxicita MeSH
- potkani Wistar MeSH
- regulace genové exprese enzymů MeSH
- thioredoxinreduktasa 2 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- 4-hydroxy-2-nonenal MeSH Prohlížeč
- aldehyddehydrogenasa MeSH
- aldehydy MeSH
- antibiotika antitumorózní MeSH
- apoferritin doxorubicin MeSH Prohlížeč
- apoferritiny MeSH
- biologické markery MeSH
- doxorubicin MeSH
- liposomal doxorubicin MeSH Prohlížeč
- polyethylenglykoly MeSH
- thioredoxinreduktasa 2 MeSH
- Txnrd2 protein, rat MeSH Prohlížeč
- Klíčová slova
- PNEUMOPERITONEUM, ARTIFICIAL *,
- MeSH
- lidé MeSH
- pneumoperitoneum umělé * MeSH
- pneumoperitoneum * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- DUODENUM/neoplasms *,
- MeSH
- diferenciální diagnóza * MeSH
- duodenum * MeSH
- lidé MeSH
- nádory duodena * MeSH
- nádory * MeSH
- sekundární malignity * MeSH
- tenké střevo * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Sbornik pro pathofysiologii traveni a vyzivy; gastroenterologia bohema | Sb Pathofysiol Traveni Vyz Gastroenterol Bohema
Zdroj
- Klíčová slova
- LIVER CIRRHOSIS/complications *, OSTEOPOROSIS/etiology and pathogenesis *,
- MeSH
- jaterní cirhóza komplikace MeSH
- lidé MeSH
- osteoporóza etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- EMPHYSEMA, PULMONARY *,
- MeSH
- emfyzém * MeSH
- plicní emfyzém * MeSH
- Publikační typ
- časopisecké články MeSH