We describe a conceptually new, microfibrous, biodegradable functional material prepared from a modified storage polysaccharide also present in humans (glycogen) showing strong potential as direct-contact dressing/interface material for wound healing. Double bonds were introduced into glycogen via allylation and were further exploited for crosslinking of the microfibers. Triple bonds were introduced by propargylation and served for further click functionalization of the microfibers with bioactive peptide. A simple solvent-free method allowing the preparation of thick layers was used to produce microfibers (diameter ca 2μm) from allylated and/or propargylated glycogen. Crosslinking of the samples was performed by microtron beta-irradiation, and the irradiation dose was optimized to 2kGy. The results from biological testing showed that these highly porous, hydrophilic, readily functionalizable materials were completely nontoxic to cells growing in their presence. The fibers were gradually degraded in the presence of cells.
- MeSH
- biomimetické materiály chemická syntéza chemie farmakologie MeSH
- glykogen chemie MeSH
- kultivované buňky MeSH
- lidé MeSH
- obvazy * MeSH
- osteoblasty účinky léků fyziologie MeSH
- polymery chemická syntéza chemie MeSH
- testování materiálů MeSH
- vstřebatelné implantáty * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Auger electrons-emitting radioisotopes (such as iodine-125) are a potentially effective cancer treatment. They are extremely biologically effective, but only within a short range (nanometers). Their use as an effective cancer therapy requires that they will be transported within close proximity of DNA by an intercalator, where they induce double-strand breaks leading to cell death. This type of therapy may be even more beneficial when associated with drug delivery systems. In this report, we describe an optimized triple-targeted polymer delivery system for the intercalator ellipticine, which contains radioisotope iodine-125 with high specific radioactivity (63.2 GBq/mg). This compound is linked to an N-(2-hydroxypropyl)methacrylamide copolymer via an optimized acid-sensitive hydrazone linker. The system is stable at pH 7.4 (representing the pH of blood plasma), and the radioiodine-containing biologically active intercalator is released upon a decrease in pH (44% of the intercalator is released after 24h of incubation in pH 5.0 buffer, which mimics the pH in late endosomes). The active compound is a potent intercalator, as shown with direct titration with a DNA solution, and readily penetrates into cell nuclei, as observed by confocal microscopy. Its polymer conjugate is internalized into endosomes and releases the radioactive intercalator, which accumulates in the cell nuclei. In vivo experiments on mice with 4T1 murine breast cancer resulted in a statistically significant increase in the survival of mice treated with the polymer radioconjugate. The free radiolabeled intercalator was also shown to be effective, but it was less potent than the polymer conjugate.
- MeSH
- antitumorózní látky chemie farmakologie MeSH
- elektrony * MeSH
- elipticiny chemie farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- léky antitumorózní - screeningové testy MeSH
- molekulární struktura MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nádory prsu farmakoterapie patologie MeSH
- polymery chemická syntéza chemie MeSH
- radioizotopy jodu MeSH
- systémy cílené aplikace léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
