RESUMO
Polymer conjugation has been widely used to improve the stability and pharmacokinetics of therapeutic biomacromolecules; however, conventional methods to generate such conjugates often use disperse and/or achiral polymers with limited functionality. The heterogeneity of such conjugates may lead to manufacturing variability, poorly controlled biological performance, and limited ability to optimize structure-property relationships. Here, using insulin as a model therapeutic polypeptide, we introduce a strategy for the synthesis of polymer-protein conjugates based on discrete, chiral polymers synthesized through iterative exponential growth (IEG). These conjugates eliminate manufacturing variables originating from polymer dispersity and poorly controlled absolute configuration. Moreover, they offer tunable molecular features, such as conformational rigidity, that can be modulated to impact protein function, enabling faster or longer-lasting blood glucose responses in diabetic mice when compared to PEGylated insulin and the commercial insulin variant Lantus. Furthermore, IEG-insulin conjugates showed no signs of decreased activity, immunogenicity, or toxicity following repeat dosing. This work represents a significant step toward the synthesis of precise synthetic polymer-biopolymer conjugates and reveals that fine tuning of synthetic polymer structure may be used to optimize such conjugates in the future.
Assuntos
Diabetes Mellitus Experimental , Polímeros , Animais , Camundongos , Polímeros/química , Diabetes Mellitus Experimental/tratamento farmacológico , Proteínas/químicaRESUMO
Digital polymers with precisely arranged binary units provide an important option for information storage. This is especially true if the digital polymers are assembled in a device, as it would be of great benefit for data writing and reading in practice. Herein, inspired by the DNA microarray technique, the programmable information storing and reading on a mass spectrometry target plate is proposed. First, an array of 4-bit sequence-coded dithiosuccinimide oligomers is efficiently built through sequential thiol-maleimide Michael couplings with good sequence readability by tandem mass spectrometry (MS/MS). Then, toward engineering microarrays for information storage, a programmed robotic arm is specifically designed for precisely loading sequence-coded oligomers onto the target plate, and a decoding software is developed for efficient readout of the data from MS/MS sequencing. Notably, short sequence-coded oligomer chains can be used to write long strings of information, and extra error-correction codes are not required as usual due to the inherent concomitant fragmentation signals. Not only text but also bitimages can be automatically stored and decoded with excellent accuracy. This work provides a promising platform of digital polymers for programmable information storing and reading.
Assuntos
Polímeros , Espectrometria de Massas em Tandem , Polímeros/química , Espectrometria de Massas em Tandem/métodosRESUMO
Sequence control has attracted increasing attention for its ability of regulating polymer property and performance. Herein, the sequence-controlled polymer containing acrylonitrile (AN) is achieved by using 2,5-dimethylfuran/acrylonitrile adduct as a latent monomer. The temperature-dependent retro Diels-Alder reaction is engaged in controlling the release of AN during RAFT polymerization, that is, regulating the instant AN concentration via a non-invasive and in situ manner. Such control over the instant AN concentration and particularly the molar ratio of comonomer pair leads to the simultaneous change of monomer units in "living" polymeric chain, thus resulting in the sequence-controlled polymeric structures. By delicately manipulating the polymerization temperature, diverse sequence-on-demand structures of AN-containing copolymers, such as poly(AN/methyl methacrylate), poly(AN/styrene), poly(AN/butyl acrylate), poly(AN/N,N-dimethylacrylamide), and poly(AN/N-isopropylacrylamide) are created. Meanwhile, this study presents an initial attempt in tuning the thermal responsivity of poly(AN/N-isopropylacrylamide), which is closely correlated to the sequence of polymer structure. More importantly, the polymer with averagely distributed AN units results in the higher thermal sensitivity. Therefore, the synthetic strategy proposed in this work offers a promising platform for accessing the sequence-controlled copolymers containing AN structures, thus expanding the investigation on the relationship between the polymer structures and correlated properties.
Assuntos
Acrilonitrila , Atenção , Furanos , Polimerização , PolímerosRESUMO
Fe3O4/Polyvinylidene fluoride (PVDF) three-channel hollow fiber catalytic membrane was successfully fabricated via non-solvent induced phase inversion and used for organic wastewater degradation in this work. The effects of Fe3O4 nanoparticles addition on the surface and cross-section morphologies, hydrophilicity and thermal properties of the catalytic membrane were characterized by the field emission scanning electron microscopy (SEM), water contact angle and thermogravimetric analysis (TGA), respectively. The obtained catalytic membrane exhibited good hydrophilicity, a high pure water flux of 175.8 L m-2 h-1 and a high removal of methylene blue (up to 97.6%) with Fenton catalytic reaction. Meanwhile, the catalytic membrane shows excellent anti-fouling property due to the presence of Fenton reaction. Our results show that Fe3O4/PVDF three-channel hollow fiber catalytic membrane was a promising alternative for the degradation of organic contaminants.
Assuntos
Membranas Artificiais , Águas Residuárias , Permeabilidade , PolivinilRESUMO
Collagen's unique properties promise hemostatic potential, but its sponge form's stability and mechanics need improvement. In this study, we developed a series of homeostatic sponges by co-assembling collagen and curdlan at different ratios into hydrogels, followed by freeze-drying treatment. The incorporation of curdlan into collagen sponges has been found to significantly enhance the sponge's properties, including increased porosity, elevated water uptake, improved elasticity, and enhanced resistance to degradation. In vitro cytotoxicity and hemolysis assays have demonstrated the biocompatibility and nontoxicity of composite sponges. In mouse liver perforation and incision models, the composite sponges achieved rapid coagulation within 67 s and 75 s, respectively, outperforming gauze and gelatin sponge in reducing blood loss. Furthermore, composite sponges demonstrated superior wound healing potential in mice full-thickness skin defects model, with accelerated healing rates observed at days 3, 7, and 14 compared to the control group. Overall, collagen/curdlan composite sponge show promise for hemostasis and wound healing applications.
Assuntos
Colágeno , Hemostasia , Cicatrização , beta-Glucanas , Animais , Cicatrização/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , beta-Glucanas/farmacologia , beta-Glucanas/química , Camundongos , Hemostasia/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/lesões , Hidrogéis/química , Hidrogéis/farmacologia , Hemólise/efeitos dos fármacos , Hemostáticos/farmacologia , Hemostáticos/química , Porosidade , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , MasculinoRESUMO
Physicochemical properties of nanoparticles, such as particle size, surface charge, and particle shape, have a significant impact on cell activities. However, the effects of surface functionalization of nanoparticles with small chemical groups on stem cell behavior and function remain understudied. Herein, we incorporated different chemical functional groups (amino, DETA, hydroxyl, phosphate, and sulfonate with charges of +9.5, + 21.7, -14.1, -25.6, and -37.7, respectively) to the surface of inorganic silica nanoparticles. To trace their effects on mesenchymal stem cells (MSCs) of rat bone marrow, these functionalized silica nanoparticles were used to encapsulate Rhodamine B fluorophore dye. We found that surface functionalization with positively charged and short-chain chemical groups facilitates cell internalization and retention of nanoparticles in MSCs. The endocytic pathway differed among functionalized nanoparticles when tested with ion-channel inhibitors. Negatively charged nanoparticles mainly use lysosomal exocytosis to exit cells, while positively charged nanoparticles can undergo endosomal escape to avoid scavenging. The cytotoxic profiles of these functionalized silica nanoparticles are still within acceptable limits and tolerable. They exerted subtle effects on the actin cytoskeleton and migration ability. Last, phosphate-functionalized nanoparticles upregulate osteogenesis-related genes and induce osteoblast-like morphology, implying that it can direct MSCs lineage specification for bone tissue engineering. Our study provides insights into the rational design of biomaterials for effective drug delivery and regenerative medicine.
Assuntos
Materiais Biocompatíveis , Teste de Materiais , Células-Tronco Mesenquimais , Nanopartículas , Tamanho da Partícula , Dióxido de Silício , Propriedades de Superfície , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Nanopartículas/química , Animais , Ratos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Osteogênese/efeitos dos fármacosRESUMO
Chirality and molecular conformation are central components of life: biological systems rely on stereospecific interactions between discrete (macro)molecular conformers, and the impacts of stereochemistry and rigidity on the properties of small molecules and biomacromolecules have been intensively studied. Nevertheless, how these features affect the properties of synthetic macromolecules has received comparably little attention. Here we leverage iterative exponential growth and ring-opening metathesis polymerization to produce water-soluble, chiral bottlebrush polymers (CBPs) from two enantiomeric pairs of macromonomers of differing rigidity. Remarkably, CBPs with conformationally flexible, mirror image side chains show several-fold differences in cytotoxicity, cell uptake, blood pharmacokinetics and liver clearance; CBPs with comparably rigid, mirror image side chains show no differences. These observations are rationalized with a simple model that correlates greater conformational freedom with enhanced chiral recognition. Altogether, this work provides routes to the synthesis of chiral nanostructured polymers and suggests key roles for stereochemistry and conformational rigidity in the design of future biomaterials.
Assuntos
Polímeros/química , Conformação Molecular , EstereoisomerismoRESUMO
FexOy@FexOy/C nanoparticles with a soap-bubble-like shell have been synthesized, and the materials exhibit excellent Fenton catalytic performance. More importantly, FexOy@FexOy/C nanoparticles as catalysts and precursors could catalyze organic dye molecules to form iron oxide@organic dye polymer core-shell nanospheres.