Novel multiresponsive hybrid biocompatible systems of κ-carrageenan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline)s with unique combination of responsiveness to external stimuli were synthesized and studied. The polymer thermoresponsive behavior proved the existence of both lower and upper critical solution temperatures in aqueous milieu, forming gel at lower temperature, a solution at room temperature and cloudy nanophase-separated dispersion at elevated temperature. The limit temperatures can easily be adjusted by the polyoxazoline graft length and grafting density. Moreover, the polymer behavior is additionally dependent on the concentration of potassium ions. The polymers behave similarly as the original κ-carrageenan, and thus, the poly(2-alkyl-2-oxazoline) grafts do not decrease the ability of the κ-carrageenan to form the self-assembled structures. Molecular principles beyond this multistimuli-responsive behavior were elucidated with the use of dynamic light scattering, magnetic resonance and fluorescence measurements as well as atomic force microscopy. These polymers could be used in a wide range of biological applications demanding thermo- and potassium-responsiveness.

• MeSH
• imunokonjugáty chemie   MeSH
• intravitální mikroskopie MeSH
• lymfatické uzliny diagnostické zobrazování   MeSH
• mannany * chemická syntéza   MeSH
• multimodální zobrazování * metody   MeSH
• myši MeSH
• optické zobrazování metody   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

The effective drug delivery systems for cancer treatment are currently on high demand. In this paper, biological behavior of the novel hybrid copolymers based on polysaccharide glycogen were characterized. The copolymers were modified by fluorescent dyes for flow cytometry, confocal microscopy, and in vivo fluorescence imaging. Moreover, the effect of oxazoline grafts on degradation rate was examined. Intracellular localization, cytotoxicity, and internalization route of the modified copolymers were examined on HepG2 cell line. Biodistribution of copolymers was addressed by in vivo fluorescence imaging in C57BL/6 mice. Our results indicate biocompatibility, biodegradability, and non-toxicity of the glycogen-based hybrid copolymers. Copolymers were endocyted into the cytoplasm, most probably via caveolae-mediated endocytosis. Higher content of oxazoline in polymers slowed down cellular uptake. No strong colocalization of the glycogen-based probe with lysosomes was observed; thus, it seems that the modified externally administered glycogen is degraded in the same way as an endogenous glycogen. In vivo experiment showed relatively fast biodistribution and biodegradation. In conclusion, this novel nanoprobe offers unique chemical and biological attributes for its use as a novel drug delivery system that might serve as an efficient carrier for cancer therapeutics with multimodal imaging properties.

• MeSH
• buňky Hep G2 MeSH
• endocytóza MeSH
• fluorescein-5-isothiokyanát aplikace a dávkování   farmakokinetika   MeSH
• fluorescenční barviva aplikace a dávkování   farmakokinetika   MeSH
• glykogen aplikace a dávkování   farmakokinetika   MeSH
• heterocyklické sloučeniny aplikace a dávkování   farmakokinetika   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• nosiče léků aplikace a dávkování   farmakokinetika   MeSH
• organokovové sloučeniny aplikace a dávkování   farmakokinetika   MeSH
• polyaminy aplikace a dávkování   farmakokinetika   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH