Biomacromolecules最新文献

One of the promising candidates for new antimicrobial agents is membrane-lytic compounds that kill microbes through cell membrane permeabilization, such as antimicrobial peptides (AMPs) and their synthetic mimics (SMAMPs). Although SMAMPs have been under investigation for nearly 30 years, a few challenges must be addressed before they can reach clinical use. In this work, a step-growth polymerization leading to already-known highly antimicrobial ionenes was redirected toward the formation of macrocyclic quaternary ammonium salts (MQAs) employing a high dilution principle. Antimicrobial assays and cytotoxicity studies revealed the high antimicrobial activity of MQAs and better selectivity than their polymeric analogues. Therefore, MQAs seem to be a new class of promising antibacterial agents. Additionally, membrane-lytic experiments using large unilamellar liposomes (LUVs) and whole cells revealed significant differences between MQAs and ionenes in their ability to adsorb onto the surface of LUVs and microbes as well as their ability to permeate the lipid bilayer.

The ability to design liver-targeted gene delivery vectors is plagued with difficulties ranging from carrier-mediated cellular toxicity to challenges in encapsulating sensitive nucleic acids. Herein, we present an ultrasound-responsive glycopolymersome strategy for in situ loading of nucleic acids and achieving hepatocyte-specific gene delivery. This glycopolymersome is self-assembled from a block copolymer, N-acetylgalactosamine-grafted poly(glutamic acid)-block-poly(ε-caprolactone) (PGAGalNAc-b-PCL). GalNAc is introduced to afford liver targeting through the selective binding to the asialoglycoprotein receptor overexpressed on hepatocytes. External ultrasound is utilized to assist in encapsulating nucleic acids within the hydrophilic lumen of glycopolymersomes by exploiting their ultrasound responsiveness nature. Biological studies confirmed the successful encapsulation of plasmid DNA (pDNA) and small interfering RNA (siRNA), rapid nuclear internalization, and efficient gene transfection. These findings collectively demonstrated that this ultrasound-responsive glycopolymersome could be exploited as a novel safe and efficient gene vector targeting hepatocytes.

Under 3D culture conditions, cells tend to spread, migrate, and proliferate better in more viscoelastic and plastic hydrogels. Here, we present evidence that the improved cell behavior is facilitated by the lower steric hindrance of a more viscoelastic and plastic matrix with weaker intermolecular bonds. To determine intermolecular bond stability, we slowly insert semispherical tipped needles (100-700 μm diameter) into alginate dialdehyde-gelatin hydrogels and measure stiffness, yield strength, plasticity, and the force at which the surface ruptures (puncture force). To tune these material properties without affecting matrix stiffness, we precross-link the hydrogels with CaCl₂ droplets prior to mixing in NIH/3T3 fibroblasts and final cross-linking with CaCl₂. Precross-linking introduces microscopic weak spots in the hydrogel, increases plasticity, and decreases puncture force and yield strength. Fibroblasts spread and migrate better in precross-linked hydrogels, demonstrating that intermolecular bond stability is a critical determinant of cell behavior under 3D culture conditions.

This study presents the development and characterization of a novel porphyrin-Jeffamine polymer conjugate designed to function as a photosensitizer prodrug for antimicrobial photodynamic therapy (aPDT). The conjugate features a photosensitive porphyrin unit covalently attached to a biocompatible polymer backbone, with enhanced solubility, stability, and bioavailability compared to those of the free porphyrin derivatives. The photophysical properties were studied using transient absorption spectroscopy spanning the fs-μs time scales in addition to emission studies. The production of reactive oxygen species upon photoactivation enabled effective bacterial cell killing. Spectroscopic studies confirmed strong binding of the conjugate to DNA through intercalation, likely disrupting DNA replication and transcription. Interaction studies with bovine serum albumin demonstrated substantial serum protein binding, which may positively impact the pharmacokinetics and biodistribution. Overall, this porphyrin-polymer conjugate offers a multifunctional theranostic platform, combining antimicrobial action with DNA and protein binding potential, positioning it as a promising candidate for aPDT and bioimaging applications.

Polymers with hemiacetal esters integrated in their backbone provide beneficial degradation profiles for (immuno-) drug delivery. However, their fast hydrolysis and low drug loading capacity have limited their applications so far. Therefore, this study focuses on the stability and loading capacity of hemiacetal ester polymers. The hydrophobicity of the micellar core has a tremendous effect on the hemiacetal ester stability. For that purpose, we introduce a new monomer with a phenyl moiety for stabilizing the micellar core and improving drug loading. The carrier functionality can further be expanded by post-polymerization modifications via activated ester groups at the polymer chain end. This allows for covalent dye labeling, which provides substantial insights into the polymers' in vitro performance. Flow cytometric analyses on RAW dual macrophages revealed intact micelles exhibiting significantly higher cellular uptake compared to degraded species, thus, highlighting the potential of end group functionalized poly(hemiacetal ester)s for (immuno)drug delivery purposes.

The development of sustainable materials has driven significant interest in starch as a renewable and biodegradable polymer. However, the inherent brittleness, hydrophilicity, and lack of thermoplasticity of native starch limit its application in material science. This study addresses the limitations of native starch by converting it to dialdehyde starch (DAS) and cross-linking with polyether diamines via imine bonds. The effects of Jeffamine molecular weights (D-2000, D-400, and D-230) and mole ratios on the mechanical, thermal, and structural properties of starch-based films were examined. The cross-linked DAS/Js films exhibited significant enhancements in flexibility and toughness. Specifically, DAS/J2000 at a 0.03 mol ratio achieved a tensile strength of 62.9 MPa. In comparison, DAS/J400 at a 0.5 mol ratio demonstrated 126.2% elongation at break, indicating the balance between cross-linking density and chain mobility. X-ray diffraction (XRD) analysis revealed reduced crystallinity and tighter molecular packing with increased cross-linking. Dynamic mechanical analysis (DMA) indicated a decrease in Tg with an increasing mole ratio, reflecting enhanced molecular mobility. The results underscore the potential of optimized cross-linking conditions to produce starch-based films with properties that contribute to developing sustainable biopolymer materials.

Four biobased phosphate-containing aryl monomers with methoxy, allyl, and vinyl groups as substituents have been successfully synthesized. Copolymerizing these monomers with thiophenol or mercaptans via the photoclick thiol-ene reaction gives the polymers with refractive indices (n_D) of 1.63-1.70 and Abbe numbers (v_D) of 12.8-38.5. An investigation of the relationship of the v_D values with the substituents on the benzene rings of the monomers indicates that methoxy and vinyl groups can collectively increase the v_D values. In comparison with allyl groups, vinyl groups endow the polymers with both higher n_D and v_D. Moreover, these polymers also display high transmittance, high thermostability, and low haze values in the visible-light region, suggesting that these biobased functional monomers are satisfactory precursors used in the fabrication of optical devices.

This study investigates the use of pH-responsive nanogels for delivering Bosutinib (BOSU) in colon cancer treatment. Nanogels were formulated using three polymers: hyaluronic acid (HA), carboxymethyl dextran (CMD), and gelatin methacryloyl (GelMA). These nanogels achieved high drug entrapment efficiencies (80-90%) through polymer mixing with BOSU, followed by EDC/NHS cross-linking and sonication. The nanogels were stable, with negative zeta potentials (-20 to -30 mV) and particle sizes between 100 and 200 nm. Fourier-transform infrared analysis confirmed successful methacrylation in GelMA nanogels. Sustained BOSU release at pH 5.0 was observed, resembling tumor environments, compared to slower release at normal pH (7.4). Cytotoxicity tests showed 70-80% cell survival reduction in HCT116 colon cancer cells at higher doses, and GelMA-BOSU nanogels notably reduced cell migration. Antiangiogenic effects were confirmed in a chick chorioallantoic membrane model, highlighting the potential of these nanogels for targeted BOSU delivery in colon cancer therapy.

The precise modulation of protein-carbohydrate interactions is critical in glycobiology, where multivalent binding governs key cellular processes. As such, synthetic glycopolymers are useful for probing these interactions. Herein, we developed precision glycopolymers (PGPs) with unambiguous local chemical composition and well-defined global structure and systematically evaluated the effect of polymer length, hydrophobicity, and backbone hybridization as well as glycan density and identity on the binding to both mammalian and plant lectins. Our studies identified glycan density as a critical factor, with PGPs below 50% grafting density showing significantly weaker lectin interactions. Coarse-grained molecular dynamics simulations suggest that the observed phenomena may be due to a decrease in carbohydrate-carbohydrate interactions in fully grafted PGPs, leading to improved solvent accessibility. In functional assays, these PGPs reduced the cell viability and migration in 4T1 breast cancer cells. Our findings establish a structure-activity relationship in glycopolymers, providing new strategies for designing synthetic glycomacromolecules for a myriad of applications.

We prepared biocompatible elastic fibers with high porosity and high tensile strength from poly[(R)-3-hydroxybutyrate-co-4-hydroxybutyrate], which is a microbial polyester that can be produced from renewable carbon resources by isothermal crystallization. It was possible to control the pore size by adjusting the isothermal crystallization time. Most of the pores were approximately less than 10 μm in diameter, did not penetrate, and were distributed discontinuously throughout the fibers. The elasticity of the fibers was apparently attributable to the generation of tie molecules with planar zigzag conformations between lamellar crystals and to the deformation of the pores. The ligature area occupied by the porous fibers in surgical knots was reduced by 75% compared with that of nonporous fibers. This is expected to make the ligature more difficult to untie and reduce the feeling of foreign matter. X-ray tomography revealed that the porous fibers had a relatively small fiber diameter owing to the collapse of the porous area. The rate of enzymatic degradation of the porous fibers was more than four times that of nonporous fibers. These results suggest that this elastic porous fiber will have many applications, including in the medical and marine material fields.