Efficient Catalyst-Free One-Pot Synthesis of Polysaccharide-Polypeptide Hydrogels in Aqueous Solution.

The preparation of polysaccharide-peptide hydrogels usually involves multiple synthetic steps, thus reducing the effectiveness and practicality of these approaches. Inspired by recent discoveries in aqueous N-carboxyanhydride (NCA) ring-opening polymerization (ROP) and ring-opening polymerization-induced nanogelation, we present an aqueous one-pot strategy to prepare polysaccharide-polypeptide hydrogels. In this study, water-soluble polysaccharide carboxymethyl chitosan is used as the macromolecular initiator to prepare polysaccharide-polypeptide copolymers through the aqueous ROP of NCA. The catalyst-free approach afforded hydrogels with properties that could be controlled by adjusting the type and amount of NCA used, with the elastic modulus ranging from 50 Pa to 18000 Pa. The hydrogen bond-cross-linked hydrogel exhibited self-healing and injectable properties. Morphology characterization revealed that micelles were formed in the early stage of reaction, suggesting that the polymerization follows an aqueous ring-opening polymerization-induced self-assembly (ROPISA) mechanism and that aggregation of micelles during the reaction caused the gelation. Moreover, the hydrogels displayed high swelling ratios (>95% water content), and hemolysis and cytotoxicity experiments demonstrated that the hydrogels had excellent biocompatibility, indicating their potential in medical applications.

Dextran Macroinitiator for Synthesis of Polysaccharide-b-Polypeptide Block Copolymers via NCA Ring-Opening Polymerization.

Synthesis of polysaccharide-b-polypeptide block copolymers represents an attractive goal because of their promising potential in delivery applications. Inspired by recent breakthroughs in N-carboxyanhydride (NCA) ring-opening polymerization (ROP), we present an efficient approach for preparation of a dextran-based macroinitiator and the subsequent synthesis of dextran-b-polypeptides via NCA ROP. This is an original approach to creating and employing a native polysaccharide macroinitiator for block copolymer synthesis. In this strategy, regioselective (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of the sole primary alcohol located at the C-6 position of the monosaccharide at the nonreducing end of linear dextran results in a carboxylic acid. This motif is then transformed into a tetraalkylammonium carboxylate, thereby generating the dextran macroinitiator. This macroinitiator initiates a wide range of NCA monomers and produces dextran-b-polypeptides with a degree of polymerization (DP) of the polypeptide up to 70 in a controlled manner (D < 1.3). This strategy offers several distinct advantages, including preservation of the original dextran backbone structure, relatively rapid polymerization, and moisture tolerance. The dextran-b-polypeptides exhibit interesting self-assembly behavior. Their nanostructures have been investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and adjustment of the structure of block copolymers allows self-assembly of spherical micelles and worm-like micelles with varied diameters and aspect ratios, revealing a range of diameters from 60 to 160 nm. Moreover, these nanostructures exhibit diverse morphologies, including spherical micelles and worm-like micelles, enabling delivery applications.

Desilylation Induced by Metal Fluoride Nanocrystals Enables Cleavage Chemistry In Vivo.

Metal fluoride nanocrystals are widely used in biomedical studies owing to their unique physicochemical properties. The release of metal ions and fluorides from nanocrystals is intrinsic due to the solubility equilibrium. It used to be considered as a drawback because it is related to the decomposition and defunction of metal fluoride nanocrystals. Many strategies have been developed to stabilize the nanocrystals, and the equilibrium concentrations of fluoride are often <1 mM. Here we make good use of this minimum amount of fluoride and unveil that metal fluoride nanocrystals could effectively induce desilylation cleavage chemistry, enabling controlled release of fluorophores and drug molecules in test tubes, living cells, and tumor-bearing mice. Biocompatible PEG (polyethylene glycol)-coated CaF2 nanocrystals have been prepared to assay the efficiency of desilylation-induced controlled release of functional molecules. We apply the strategy to a prodrug activation of monomethyl auristatin E (MMAE), showing a remarkable anticancer effect, while side effects are almost negligible. In conclusion, this desilylation-induced cleavage chemistry avails the drawback on empowering metal fluoride nanocrystals with a new function of perturbing or activating for further biological applications.

Selective Oxidation of 2-Hydroxypropyl Ethers of Cellulose and Dextran: Simple and Efficient Introduction of Versatile Ketone Groups to Polysaccharides.

Oxidation of polysaccharides has been a useful approach to new materials. However, selectivity in oxidation of polysaccharide macromolecular polyols remains a significant challenge with few methods for the synthesis of ketone-substituted polysaccharides. We report here a selective, practical, and efficient process, beginning with 2-hydroxypropyl ethers of polysaccharides that are simple and economical to prepare. We demonstrate this approach herein using commercial 2-hydroxypropyl cellulose (HPC) and 2-hydroxypropyl dextran (HPD) that we prepared. We oxidize the terminal, secondary alcohols of the oligo(2-hydroxypropyl) substituents with sodium hypochlorite so that the product has an oligo(2-hydroxypropyl) side chains terminated by a ketone. We demonstrate the high chemo- and regioselectivity of this oxidation by analytical methods including hydrolysis to monosaccharides and mass spectrometry of the resulting mixture. We provide an initial demonstration of the potential utility of these keto-polysaccharides by reacting Ox-HPC with primary amines to form Schiff base imines, providing proactive polymers.

Regioselective Bromination of the Dextran Nonreducing End Creates a Pathway to Dextran-Based Block Copolymers.

Preparation of polysaccharide-based block copolymers with linear architectures is an important goal, opening up clear application potential and requiring significant advances in polysaccharide regio- and chemoselectivity. Herein we report a simple approach to prepare dextran-based block copolymers. Reaction with N-bromosuccinimide (NBS)/triphenyl phosphine (PPh3) regioselectively brominates the sole primary alcohol of linear, unbranched dextran at C-6 of the nonreducing end monosaccharide. The resulting dextran, monofunctionalized with a terminal C-6 bromide, was coupled with various amine terminated polymers to prepare block copolymers, including dextran-b-poly(ethylene glycol), dextran-b-polystyrene, and dextran-b-poly(N-isopropylacrylamide). These renewable-based block copolymers, prepared in two selective, high-yielding steps from native linear dextran, exhibit various interesting properties. Dextran-b-poly(N-isopropylacrylamide) undergoes thermally induced micellization as revealed by dynamic light scattering (DLS), forming micelles upon exceeding 33 °C. We also observed microphase separation in dextran-b-polystyrene by using small-angle X-ray scattering (SAXS). Overall, this methodology provides a new, highly chemo- and regioselective, versatile route to diverse dextran-based block copolymers with useful properties, enabling drug delivery, compatibilization, and other applications.

Dess-Martin oxidation of hydroxypropyl and hydroxyethyl cellulose, and exploration of their polysaccharide/polypeptide hydrogels.

Oxidation of polysaccharides can provide biomaterials with aldehyde and ketone functional groups, which are particularly useful in biomedical applications, like drug delivery, tissue adhesion and hydrogel preparation. However, despite their potential, only a few such methods have been reported, and achieving selective, quantitative oxidation of polysaccharides remains challenging. Herein we report utilization of a mild oxidant, Dess-Martin periodinane, for the chemoselective oxidation of hydroxypropyl cellulose (HPC) and hydroxyethyl cellulose (HEC). Our findings reveal that the oxidation of HPC is fast, efficient and achieves near-quantitative conversion. Moreover, both Ox-HPC and Ox-HEC exhibit low cell toxicity, and readily form hydrogels by reaction with a polypeptide comprising amino acids with amine-containing a-substituents, α-poly-l-lysine. The peptide/polysaccharide hydrogels display self-healing properties, injectability, and antimicrobial activity, making them highly attractive for biomedical applications including in wound dressings.

Facile preparation of biocompatible and antibacterial water-soluble films using polyvinyl alcohol/carboxymethyl chitosan blend fibers via centrifugal spinning.

Water-soluble polyvinyl alcohol/carboxymethyl chitosan (PVA/CMCS) blend fiber films were successfully prepared using a plane-collection centrifugal spinning machine. The addition of CMCS significantly increased the shear viscosity of the PVA/CMCS blend solution. The effects of spinning temperature on the shear viscosity and the centrifugal spinnability of PVA/CMCS blend solution were discussed. The PVA/CMCS blend fibers were uniform, and their average diameters ranged from 1.23 µm to 29.01 µm. It was found that the CMCS was distributed evenly in the PVA matrix and increased the crystallinity of PVA/CMCS blend fiber films. The hydrogen bonds between the hydroxyl group of PVA and the carboxymethyl group of CMCS were also detected. An in vitro cell study of human skin fibroblast cells on the PVA/CMCS blend fiber films confirmed biocompatibility. The maximum tensile strength and elongation at break of PVA/CMCS blend fiber films could reach 3.28 MPa and 29.52 %, respectively. The colony-plate-count tests indicated that the PVA16-CMCS2 presented 72.05 % and 21.36 % antibacterial rates against Staphylococcus aureus (104 CFU/mL) and Escherichia coli (103 CFU/mL), respectively. These values indicated that the newly prepared PVA/CMCS blend fiber films are promising materials for cosmetic and dermatological applications.

Fully-branched hyperbranched polymers with a diselenide core as glutathione peroxidase mimics.

A novel glutathione peroxidase (GPx) mimic has been prepared by incorporation of a selenium-based catalytic unit into the focal point of a fully-branched hyperbranched polymer. First, an AB(2) monomer consisting of isatin and an electron rich aromatic moiety was polycondensed in the presence of 5-nitroisatin as a core reagent, resulting in a polymer with 100% degree of branching. The latter was coupled to the catalytically active moiety, Br(CH(2))(5) SeSe(CH(2))(5) Br, by nucleophilic substitution of the bromides by the residual amide groups of the incorporated nitroisatin core. The obtained polymer has demonstrated prominent GPx activity as desired, which could be attributed to the hydrophobic, densely branched and core-shell structure of the polymer surrounding the catalytic center.

A comparative study on adsorption and catalytic degradation of tetracycline by five magnetic mineral functional materials prepared from steel pickling waste liquor.

Palygorskite (Pal), bentonite (Bent), sepiolite (Sep), zeolite (Zeol), and kaolin (Kaol) were used with steel pickling waste liquor to synthesize magnetic palygorskite (Pal@Fe3O4), magnetic bentonite (Bent@Fe3O4), magnetic sepiolite (Sep@Fe3O4), magnetic zeolite (Zeol@Fe3O4), and magnetic kaolin (Kaol@Fe3O4), for adsorption and catalytic degradation of tetracycline (TC), respectively. Through the study of adsorption kinetics and adsorption isotherms, the maximum adsorption capacity of Pal@Fe3O4 to TC was 149.439 mg/g, which was 1.239 times, 2.260 times, 3.161 times, and 3.448 times of Bent@Fe3O4, Zeol@Fe3O4, Kaol@Fe3O4, and Sep@Fe3O4, respectively. The kinetic study of tetracycline degradation demonstrated that the maximum reaction rate constant of Bent@Fe3O4/H2O2 system was K(obs) = 2.12 × 10-2 min-1, which was close to that of Pal@Fe3O4/H2O2, Kaol@Fe3O4/H2O2 system, and was 2.000 times, 2.356 times, 2.650 times, and 4.711 times of Fe3O4/H2O2, Zeol@Fe3O4/H2O2, Sep@Fe3O4/H2O2, and H2O2 system, respectively. The results showed that Pal@Fe3O4 and Bent@Fe3O4 were more advantageous in the treatment of wastewater containing tetracycline, and efficient reuse of exhausted magnetic minerals and deep mineralization of organic pollutants were achieved by constructing an advanced oxidation system. The BET, VSM, SEM, XPS, XRD, and FTIR were used to characterize the five clay minerals before and after magnetic modification. It was speculated that the surface structure - OH groups of clay minerals might be significant factors influencing the adsorption performance of magnetic minerals on TC, and reduction ability of clay minerals to Fe3+ importantly affected the catalytic performance of magnetic minerals. The specific surface area and morphological structure of clay minerals both affected the adsorption and catalytic degradation of TC by the five magnetic minerals.

Recent advances in polysaccharide-based in situ forming hydrogels.

Polysaccharides comprise an important class of natural polymers; they are abundant, diverse, polyfunctional, typically benign, and are biodegradable. Using polysaccharides to design in situ forming hydrogels is an attractive and important field of study since many polysaccharide-based hydrogels exhibit desirable characteristics including self-healing, responsiveness to environmental stimuli, and injectability. These characteristics are particularly useful for biomedical applications. This review will discuss recent discoveries in polysaccharide-based in situ forming hydrogels, including network architecture designs, curing mechanisms, physical and chemical properties, and potential applications.

A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy.

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine-polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.