Supramolecular hydrogels that are based on inclusion complexes between α-cyclodextrin and (co)polymers have gained significant attention over the last decade. They are formed via dynamic noncovalent ...bonds, such as host-guest interactions and hydrogen bonds, between various building blocks. In contrast to typical chemical crosslinking (covalent linkages), supramolecular crosslinking is a type of physical interaction that is characterized by great flexibility and it can be used with ease to create a variety of "smart" hydrogels. Supramolecular hydrogels based on the self-assembly of polypseudorotaxanes formed by a polymer chain "guest" and α-cyclodextrin "host" are promising materials for a wide range of applications. α-cyclodextrin-based polypseudorotaxane hydrogels are an attractive platform for engineering novel functional materials due to their excellent biocompatibility, thixotropic nature, and reversible and stimuli-responsiveness properties. The aim of this review is to provide an overview of the current progress in the chemistry and methods of designing and creating α-cyclodextrin-based supramolecular polypseudorotaxane hydrogels. In the described systems, the guests are (co)polymer chains with various architectures or polymeric nanoparticles. The potential applications of such supramolecular hydrogels are also described.
Based on the Warburg effect and the increased demand for glucose by tumor cells, a targeted drug delivery strategy was developed. A series of new glycoconjugates with increased ability to interact ...with GLUT transporters, responsible for the transport of sugars to cancer cells, were synthesized. Glycoconjugation was performed using the C-6 position in the sugar unit, as the least involved in the formation of hydrogen bonds with various aminoacids residues of the transporter. The carbohydrate moiety was connected with the 8-hydroxyquinoline scaffold via a 1,2,3-triazole linker. For the obtained compounds, several in vitro biological tests were performed using HCT-116 and MCF-7 cancer cells as well as NHDF-Neo healthy cells. The highest cytotoxicity of both cancer cell lines in the MTT test was noted for glycoconjugates in which the triazole-quinoline was attached through the triazole nitrogen atom to the d-glucose unit directly to the carbon at the C-6 position. These compounds were more selective than the analogous glycoconjugates formed by the C-1 anomeric position of d-glucose. Experiments with an EDG inhibitor have shown that GLUTs can be involved in the transport of glycoconjugates. The results of apoptosis and cell cycle analyses by flow cytometry confirmed that the new type of glycoconjugates shows pro-apoptotic properties, without significantly affecting changes in the distribution of the cell cycle. Moreover, glycoconjugates were able to decrease the clonogenic potential of cancer cells, inhibit the migration capacity of cells and intercalate with DNA.
Small molecule nitrogen heterocycles are very important structures, widely used in the design of potential pharmaceuticals. Particularly, derivatives of 8-hydroxyquinoline (8-HQ) are successfully ...used to design promising anti-cancer agents. Conjugating 8-HQ derivatives with sugar derivatives, molecules with better bioavailability, selectivity, and solubility are obtained. In this study, 8-HQ derivatives were functionalized at the 8-OH position and connected with sugar derivatives (D-glucose or D-galactose) substituted with different groups at the anomeric position, using copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC). Glycoconjugates were tested for inhibition of the proliferation of cancer cell lines (HCT 116 and MCF-7) and inhibition of β-1,4-galactosyltransferase activity, which overexpression is associated with cancer progression. All glycoconjugates in protected form have a cytotoxic effect on cancer cells in the tested concentration range. The presence of additional amide groups in the linker structure improves the activity of glycoconjugates, probably due to the ability to chelate metal ions present in many types of cancers. The study of metal complexing properties confirmed that the obtained glycoconjugates are capable of chelating copper ions, which increases their anti-cancer potential.
The feasibility of synthesis of functionalized poly(3-hydroxybutanoic acid) analogue and its copolymers via ring-opening polymerization of β-butyrolactone mediated by activated anionic initiators is ...presented. Using these new synthetic approaches, polyesters with a defined chemical structure of the end groups, as well as block, graft, and random copolymers, have been obtained and characterized by modern instrumental techniques, with special emphasis on ESI-MS. The relationship between the structure and properties of the prepared polymeric materials is also discussed.
The design of prodrugs is one of the important strategies for selective anti-cancer therapies. When designing prodrugs, attention is paid to the possibility of their targeting tumor-specific markers ...such as proteins responsible for glucose uptake. That is why glycoconjugation of biologically active compounds is a frequently used strategy. Glycoconjugates consisting of three basic building blocks: a sugar unit, a linker containing a 1,2,3-triazole ring, and an 8-hydroxyquinoline fragment was described earlier. It is not known whether their cytotoxicity is due to whole glycoconjugates action or their metabolites. To check the biological activity of products that can be released from glycoconjugates under the action of hydrolytic enzymes, the synthetically obtained potential metabolites were tested in vitro for the inhibition of proliferation of HCT-116, MCF-7, and NHDF-Neo cell lines using the MTT assay. Research shows that for the full activity of glycoconjugates, the presence of all three building blocks in the structure of a potential drug is necessary. For selected derivatives, additional tests of targeted drug delivery to tumor cells were carried out using polymer nanocarriers in which they are encapsulated. This approach significantly lowered the determined IC
values of the tested compounds and improved their selectivity and effectiveness.
This paper presents basic methods of starch chemical modification, the effect of microwave radiation on the modification process, and the physicochemical properties of starch. It has been shown that ...the modifications contribute to improvement of the material performance and likewise to significant improvement of its mechanical properties. As a result, more and more extensive use of starch is possible in various industries. In addition, methods of oxidized starch and starch esters preparation are discussed. Properties of microwave radiation and its impact on starch (with particular regard to modifications described in literature) are characterized.
It was shown that selected sodium phenoxide derivatives with different basicity and nucleophilicity, such as sodium
-nitrophenoxide,
-chlorophenoxide, 1-napthoxide, phenoxide and
-methoxyphenoxide, ...are effective initiators in anionic ring-opening polymerization (AROP) of
-butyrolactone in mild conditions. It was found that phenoxides as initiators in anionic ring-opening polymerization of
-butyrolactone behave as strong nucleophiles, or weak nucleophiles, as well as Brønsted bases. The resulting polyesters possessing hydroxy, phenoxy and crotonate initial groups are formed respectively by the attack of phenoxide anion at (i) C2 followed by an elimination reaction with hydroxide formation, (ii) C4 and (iii) abstraction of acidic proton at C3. The obtained poly(3-hydroxybutyrate) possesses carboxylate growing species. The ratio of the observed initial groups strongly depends on the basicity and nucleophilicity of the sodium phenoxide derivative used as initiator. The proposed mechanism of this polymerization describes the reactions leading to formation of observed end groups. Moreover, the possibility of formation of a crotonate group during the propagation step of this polymerization is also discussed.
Nanoparticles based on amphiphilic copolymers with tunable physicochemical properties can be used to encapsulate delicate pharmaceutics while at the same time improving their solubility, stability, ...pharmacokinetic properties, reducing immune surveillance, or achieving tumor-targeting ability. Those nanocarriers based on biodegradable aliphatic polycarbonates are a particularly promising platform for drug delivery due to flexibility in the design and synthesis of appropriate monomers and copolymers. Current studies in this field focus on the design and the synthesis of new effective carriers of hydrophobic drugs and their release in a controlled manner by exogenous or endogenous factors in tumor-specific regions. Reactive groups present in aliphatic carbonate copolymers, undergo a reaction under the action of a stimulus: e.g., acidic hydrolysis, oxidation, reduction, etc. leading to changes in the morphology of nanoparticles. This allows the release of the drug in a highly controlled manner and induces a desired therapeutic outcome without damaging healthy tissues. The presented review summarizes the current advances in chemistry and methods for designing stimuli-responsive nanocarriers based on aliphatic polycarbonates for controlled drug delivery.
The development of selective delivery of anticancer drugs into tumor tissues to avoid systemic toxicity is a crucial challenge in cancer therapy. In this context, we evaluated the efficacy of a ...combination of nanocarrier pH-sensitivity and glycoconjugation of encapsulated drugs, since both vectors take advantage of the tumor-specific Warburg effect. Herein, we synthesized biodegradable diblock copolymer, a poly(ethylene glycol)-hydrazone linkage-polyR,S-3-hydroxybutyrate, which could further self-assemble into micelles with a diameter of ~55 nm. The hydrazone bond was incorporated between two copolymer blocks under an acidic pH, causing the shell-shedding of micelles which results in the drug's release. The micelles were stable at pH 7.4, but decompose in acidic pH, as stated by DLS studies. The copolymer was used as a nanocarrier for 8-hydroxyquinoline glucose and galactose conjugates as well as doxorubicin, and exhibited pH-dependent drug release behavior. In vitro cytotoxicity, apoptosis, and life cycle assays studies of blank and drug-loaded micelles were performed on Normal Human Dermal Fibroblasts-Neonatal (NHDF-Neo), colon carcinoma (HCT-116), and breast cancer (MCF-7) for 24, 48, and 72 h. A lack of toxicity of blank micelles was demonstrated, whereas the glycoconjugates-loaded micelles revealed enhanced selectivity to inhibit the proliferation of cancer cells. The strategy of combining pH-responsive nanocarriers with glycoconjugation of the drug molecule provides an alternative to the
of designing multi-stimuli nanocarriers to increase the selectivity of anticancer therapy.
The need for a cost reduction of the materials derived from (bio)degradable polymers forces research development into the formation of biocomposites with cheaper fillers. As additives can be made ...using the post-consumer wood, generated during wood products processing, re-use of recycled waste materials in the production of biocomposites can be an environmentally friendly way to minimalize and/or utilize the amount of the solid waste. Also, bioactive materials, which possess small amounts of antimicrobial additives belong to a very attractive packaging industry solution. This paper presents a study into the biodegradation, under laboratory composting conditions, of the composites that consist of poly(
)-3-hydroxybutyrate-
-4-hydroxybutyrate) and wood flour as a polymer matrix and natural filler, respectively. Thermogravimetric analysis, differential scanning calorimetry and scanning electron microscopy were used to evaluate the degradation progress of the obtained composites with different amounts of wood flour. The degradation products were characterized by multistage electrospray ionization mass spectrometry. Also, preliminary tests of the antimicrobial activity of selected materials with the addition of nisin were performed. The obtained results suggest that the different amount of filler has a significant influence on the degradation profile.
PDF
