The complexity of drug delivery mechanisms calls for the development of new transport system designs. Here, we report a robust synthetic procedure toward stable glycodendrimer (glyco-DDM) series bearing glucose, galactose, and oligo(ethylene glycol)-modified galactose peripheral units. In vitro cytotoxicity assays showed exceptional biocompatibility of the glyco-DDMs. To demonstrate applicability in drug delivery, the anticancer agent doxorubicin (DOX) was encapsulated in the glyco-DDM structure. The anticancer activity of the resulting glyco-DDM/DOX complexes was evaluated on the noncancerous (BJ) and cancerous (MCF-7 and A2780) cell lines, revealing their promising generation- and concentration-dependent effect. The glyco-DDM/DOX complexes show gradual and pH-dependent DOX release profiles. Fluorescence spectra elucidated the encapsulation process. Confocal fluorescence microscopy demonstrated preferential cancer cell internalization of the glyco-DDM/DOX complexes. The conclusions were supported by computer modeling. Overall, our results are consistent with the assumption that novel glyco-DDMs and their drug complexes are very promising in drug delivery and related applications.
- MeSH
- antitumorózní látky * farmakologie MeSH
- doxorubicin chemie farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory vaječníků * MeSH
- nosiče léků chemie MeSH
- polyethylenglykoly chemie MeSH
- silany MeSH
- systémy cílené aplikace léků metody MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The repetition of urea-based binding units within the receptor structure does not only lead to monomer properties multiplication. As confirmed by spectroscopic studies, UV-Vis and 1H-NMR in classical or competitive titration mode, the attachment to a carrier allocates the active moieties to mutual positions predetermining the function of the whole receptor molecule. Bivalent receptors form self-aggregates. Dendritic receptors with low dihydrogen phosphate loadings offer a cooperative complexation mode associated with a positive dendritic effect. In higher dihydrogen phosphate concentrations, the dendritic branches act independently and the binding mode changes to 1:1 anion: complexation site. Despite the anchoring, the dendritic receptors retain the superior efficiency and selectivity of a monomer, paving the way to recyclable receptors, desirable for economic and ecological reasons.
- MeSH
- magnetická rezonanční spektroskopie * MeSH
- molekulární modely MeSH
- sulfonamidy * MeSH
- Publikační typ
- časopisecké články MeSH
A novel approach to inducing anion transport over the dialytic membrane was proposed and successfully tested using the dihydrogen phosphate anion. The anion receptor based on isophthalamide was anchored on a dendritic skeleton, resulting in a macromolecular structure with a limited possibility to cross the dialytic membrane. The dendritic receptor was placed in a compartment separated from a mother anion solution by a membrane. The resulting anion complexation reduced the actual concentration of the anion and induced the anion transfer across the membrane. The anion concentration in mother solution decreased, while it was found to be increased in the compartment with the dendritic receptor. This phenomenon was observed using dendritic receptors with four and eight complexation sites. A detailed analysis of a series of dialytic experiments by 1H NMR spectroscopy enabled an assessment of the complexation behavior of both receptors and an evaluation of the dendritic effect on the anion complexation.
- Publikační typ
- časopisecké články MeSH
A general relationship is derived for the abundance of an imperfect dendrimer with a given number of missing constitutional repeating units in the two outmost layers. The relationship is used in the interpretation of the MALDI TOF mass spectrum of the second-generation carbosilane dendrimer prepared by the iterative divergent method. The model quantitatively describes the spectrum of the dendrimer and correctly predicts the MALDI TOF mass spectrum of its first-generation precursor. Thus, the use of well-resolved MALDI TOF mass spectra for assessing the purity of low-generation dendrimers with uniform end groups is substantiated for carbosilane dendrimers and to lesser extent for dendrimers in general.
