Polymer nanomedicines with enzymatically triggered activation: A comparative study of in vitro and in vivo anti-cancer efficacy related to the spacer structure.

Polymer nanomedicines with anti-tumor activity should exhibit sufficient stability during systemic circulation to the target tissue; however, they should release the active drug selectively in the tumor. Thus, choice of a tumor-specific stimuli-sensitive spacer between the drug and the carrier is critical. Here, a series of polymer conjugates of anti-cancer drugs doxorubicin and pirarubicin covalently bound to copolymers based on N-(2-hydroxypropyl)methacrylamide via various enzymatically cleavable oligopeptide spacers were prepared and characterized.

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

The interaction of multi-LacNAc (Galβ1-4GlcNAc)-containing -(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.

High-Affinity -(2-Hydroxypropyl)methacrylamide Copolymers with Tailored -Acetyllactosamine Presentation Discriminate between Galectins.

-Acetyllactosamine (LacNAc; Galβ4GlcNAc) is a typical disaccharide ligand of galectins. The most abundant members of these human lectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), participate in a number of pathologies including cancerogenesis and metastatic formation. In this study, we synthesized a series of fifteen -(2-hydroxypropyl)methacrylamide (HPMA)-based glycopolymers with varying LacNAc amounts and presentations and evaluated the impact of their architecture on the binding affinity to Gal-1 and Gal-3.

Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin.

Monosubstituted derivatives of γ-cyclodextrin (γ-CD) are suitable building blocks for supramolecular polymers, and can also serve as precursors for the synthesis of other regioselectively monosubstituted γ-CD derivatives. We prepared a set of monosubstituted 2--, 3--, and 6--(3-(naphthalen-2-yl)prop-2-en-1-yl) derivatives of γ-CD using two different methods. A key step of the first synthetic procedure is a cross-metathesis between previously described regioisomers of mono--allyl derivatives of γ-CD and 2-vinylnaphthalene which gives yields of about 16-25% (2-5% starting from γ-CD).

High-Strength Ultra-Fine-Grained Hypereutectic Al-Si-Fe-X (X = Cr, Mn) Alloys Prepared by Short-Term Mechanical Alloying and Spark Plasma Sintering.

In this work, Al-20Si-10Fe-6Cr and Al-20Si-10Fe-6Mn (wt %) alloys were prepared by a combination of short-term mechanical alloying and spark plasma sintering. The microstructure was composed of homogeneously dispersed intermetallic particles forming composite-like structures. X-ray diffraction analysis and TEM + EDS analysis determined that the α-Al along with α-Al(Fe,Cr)₃Si₂ or α-Al(Fe,Mn)₃Si₂ phases were present, with dimensions below 130 nm.

Influence of substituent position and cavity size of the regioisomers of monocarboxymethyl-α-, β-, and γ-cyclodextrins on the apparent stability constants of their complexes with both enantiomers of Tröger's base.

Enantiomers of Tröger's base were separated by capillary electrophoresis using 2(I) -O-, 3(I) -O-, and 6(I) -O-carboxymethyl-α-, β-, and γ-cyclodextrin and native α-, β-, and γ-cyclodextrin as chiral additives at 0-12 mmol/L for β-cyclodextrin and its derivatives and 0-50 mmol/L for α- and γ-cyclodextrins and their derivatives in a background electrolyte composed of sodium phosphate buffer at 20 mmol/L concentration and pH 2.5. Apparent stability constants of all cyclodextrin-Tröger's base complexes were calculated based on capillary electrophoresis data.

The influence of the substituent position in monocarboxymethyl-γ-cyclodextrins on enantioselectivity in capillary electrophoresis.

Three newly synthesized chiral selectors, namely, 2(I)-O-, 3(I)-O-, and 6(I)-O-carboxymethyl-γ-cyclodextrin, native γ-cyclodextrin, and commercially available carboxymethylated γ-cyclodextrin with degree of substitution of 3-6 were used as additives in a background electrolyte composed of phosphate buffer at 20 mmol/L concentration and pH 2.5. This system was used for the analysis of several biologically significant low-molecular-mass chiral compounds by capillary electrophoresis.

Complete sets of monosubstituted γ-cyclodextrins as precursors for further synthesis.

Regioselective alkylation of γ-cyclodextrin with allyl or propargyl bromide, using optimized reaction conditions, followed by peracetylation of the remaining hydroxyl groups and separation of isomers resulted in the set of peracetylated 2(I)-O-, 3(I)-O- and 6(I)-O-alkylated cyclodextrins in up to 19% yields. Ozonolysis or oxidative cleavage of peracetylated allyl derivatives resulted in a complete set of peracetylated 2(I)-O-, 3(I)-O-, and 6(I)-O-formylmethyl or -carboxymethyl derivatives. All of these derivatives are useful precursors for further preparation of regioselectively monosubstituted derivatives of γ-cyclodextrin.