Cross-Linking Effects Dictate the Preference of Galectins to Bind LacNAc-Decorated HPMA Copolymers.

The interaction of multi-LacNAc (Galß1-4GlcNAc)-containing N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers with human galectin-1 (Gal-1) and the carbohydrate recognition domain (CRD) of human galectin-3 (Gal-3) was analyzed using NMR methods in addition to cryo-electron-microscopy and dynamic light scattering (DLS) experiments. The interaction with individual LacNAc-containing components of the polymer was studied for comparison purposes. For Gal-3 CRD, the NMR data suggest a canonical interaction of the individual small-molecule bi- and trivalent ligands with the lectin binding site and better affinity for the trivalent arrangement due to statistical effects. For the glycopolymers, the interaction was stronger, although no evidence for forming a large supramolecule was obtained. In contrast, for Gal-1, the results indicate the formation of large cross-linked supramolecules in the presence of multivalent LacNAc entities for both the individual building blocks and the polymers. Interestingly, the bivalent and trivalent presentation of LacNAc in the polymer did not produce such an increase, indicating that the multivalency provided by the polymer is sufficient for triggering an efficient binding between the glycopolymer and Gal-1. This hypothesis was further demonstrated by electron microscopy and DLS methods.

Glycopolymers for Efficient Inhibition of Galectin-3: In Vitro Proof of Efficacy Using Suppression of T Lymphocyte Apoptosis and Tumor Cell Migration.

The development of efficient galectin-3 (Gal-3) inhibitors draws attention in the field of anti-cancer therapy, especially due to the prominent role of extra- and intracellular Gal-3 in vital processes of cancerogenesis, such as immunosuppression, stimulation of tumor cells proliferation, survival, invasion, apoptotic resistance, and metastasis formation and progression. Here, by combining poly-LacNAc (Galß4GlcNAc)-derived oligosaccharides with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers, we synthesized multivalent glycopolymer inhibitors with a high potential to target extracellular and intracellular Gal-3. The inhibitory capabilities of the best conjugate in the studied series were in the nanomolar range proving the excellent Gal-3 inhibitory potential. Moreover, thorough investigation of the inhibitory effect in the biological conditions showed that the glycopolymers strongly inhibited Gal-3-induced apoptosis of T lymphocytes and suppressed migration and spreading of colorectal, breast, melanoma, and prostate cancer cells. In sum, the strong inhibitory activity toward Gal-3, combined with favorable pharmacokinetics of HPMA copolymers ensuring enhanced tumor accumulation via the enhanced permeability and retention effect, nominate the glycopolymers containing LacdiNAc-LacNAc (GalNAcß4GlcNAcß3Galß4GlcNAc) tetrasaccharide as promising tools for preclinical in anti-cancer therapy evaluation.

The use of clays for chlorhexidine controlled release as a new perspective for longer durability of dentin adhesion.

The adhesive systems have the function to establish the connection between the restorative material and dental tissue, therefore it is of fundamental importance, because failures in the adhesive interface can reduce the life of a dental restoration. This study investigated the possibility of using the adhesive layer as a chlorhexidine modified release system evaluating their impact on the properties of these systems as well as evaluating the impact of these systems on immediate and post-aging dentin adhesion. Were used a matrix with BisGMA, UDMA, HEMA and TEGDMA copolymer and clay particles (Dellite 67G); associated with a chlorhexidine and a camphorquinone photoinitiator system. The properties of these systems were evaluated by the XRD, FTIR spectrophotometer, flexural strength, elasticity modulus, drug release, enzymatic inhibition and dentin adhesion resistance. The presence of the clay can raise the mechanical properties of the adhesive systems engendering a more resistant hybrid layer and led to a more sustained release of chlorhexidine in the systems, allowing a longer effective period of MMP-2 inhibition. The hypothesis that the addition of clays as release modulators could increase the effectiveness of these drugs in inhibiting the dentin's MPPs and consequently enhancing the adhesive durability was confirmed. These results indicate that the controlled release of chlorhexidine is able to reduce the process of loss of adhesion presenting itself as a promising system to increase the longevity of dental restorations.