Biomacromolecules最新文献

Biomedical polymers play a key role in preventing, diagnosing, and treating diseases, showcasing a wide range of applications. Their unique advantages, such as rich source, good biocompatibility, and excellent modifiability, make them ideal biomaterials for drug delivery, biomedical imaging, and tissue engineering. However, conventional biomedical polymers suffer from poor degradation in vivo, increasing the risks of bioaccumulation and potential toxicity. To address these issues, degradable biomedical polymers can serve as an alternative strategy in biomedicine. Degradable biomedical polymers can efficiently relieve bioaccumulation in vivo and effectively reduce patient burden in disease management. This review comprehensively introduces the classification and properties of biomedical polymers and the recent research progress of degradable biomedical polymers in various diseases. Through an in-depth analysis of their classification, properties, and applications, we aim to provide strong guidance for promoting basic research and clinical translation of degradable biomedical polymers.

An intelligent insulin delivery system targeting intestinal absorption and glucose responsiveness can enhance the bioavailability through oral insulin therapy, offering promising diabetes treatment. In this paper, a glucose and pH dual-response polymer hydrogel using carboxymethyl agarose modified with 3-amino-phenylboronic acid and l-valine (CPL) was developed as an insulin delivery carrier, exhibiting excellent biocompatibility and effective insulin encapsulation. The insulin encapsulated in the hydrogel (Ins-CPL) was released in a controlled manner in response to the in vivo stimulation of blood glucose and pH levels with higher levels of intracellular uptake and utilization of insulin in the intestinal environment simultaneously. Notably, the Ins-CPL hydrogel effectively regulated blood sugar in diabetic rats over a long period by simulating endogenous insulin, responding to changes in plasma pH and glucose levels, and overcoming the intestinal epithelium barrier. This indicates a significant boost in oral insulin bioavailability and broadens its application prospects.

Silk fibers have good biocompatibility and mechanical properties, which make them attractive in biomaterial applications as well as textile industries. It is believed that the superior mechanical property is associated with the crystalline β-sheet structure in the fiber; but a deeper understanding of the structure-property relationship is still needed for full exploitation of its physical properties. Especially, accurate information on hydrogen-bonding interactions within β-sheet domains at the nanoscale and their spatial distributions at the mesoscale are critically needed. In this study, we demonstrate the selective detection of crystalline β-sheet domains in Bombyx mori silk fiber using sum frequency generation (SFG) spectroscopy and its use to determine the angular distribution of the β-sheet crystallites with respect to the fiber axis. Numerical simulations of the SFG signal of the amide-I band were carried out using tensors based on the B2 symmetry of the D₂ point group and compared with experimental data. This comparison found that the crystalline β-sheet domains are aligned along the fiber axis with a standard deviation of ∼27° and parallel to the fiber surface with a standard deviation of ∼5°. It was also found that the amide bands in the SFG spectra cannot be fully explained with the assumption that the crystalline β-sheet vibrations can be described with the D₂ point group. Being able to monitor the amide group vibrations sensitive to both interchain hydrogen bonding and crystallite orientations, SFG analysis has a potential to unveil the structure-mechanical property relationship that may not be readily assessable with other characterization techniques.

Polyproline is a unique thermoresponsive polymer characterized by large thermal and conformational hysteresis. This article employs polyproline-based double hydrophilic block copolymers (PNIPAM_n-b-PLP_m) to gain insight into polyproline's thermoresponsive mechanism. The amine-terminated poly(N-isopropylacrylamide) (NH₂-PNIPAM_m) was used as the macroinitiator for ring-opening polymerization of proline-NCA monomers, resulting in various block copolymers (PNIPAM_n-b-PLP_m) with varying PLP block lengths. Block copolymers' thermal phase transitions were compared with their homopolymer counterparts using turbidimetry, variable-temperature NMR, dynamic light scattering, and circular dichroism spectroscopy. These experiments revealed that regardless of their compositions, all block copolymers exhibited a two-stage collapse (T_CP(PLP) > T_CP(PNIPAM)) during the heating cycle. In contrast, only one clearing temperature (T_CL) was observed during cooling. The observed clearing temperature is closely correlated to the clearing temperature of PNIPAM blocks, suggesting the role of water-soluble PNIPAM blocks in resolving the PLP blocks. Moreover, thermal and conformational hysteresis related to the polyproline block is significantly suppressed in the presence of a PNIPAM block. Linking PNIPAM blocks has two significant effects on PLP segments' thermoresponsive behavior. For example, during the heating cycle, the precollapsed PNIPAM chains (as T_CP(PNIPAM) < T_CP(PLP)) prevent orderly aggregation within the PLP block. Meanwhile, during the cooling cycle below the clearing temperature of the PNIPAM block, the PNIPAM chains impart water solubility (as T_CL(PNIPAM) > T_CL(PLP)) to the collapsed PLP chains. Overall, the PNIPAM block imparts water solubility and perturbs PLP chains to form the native aggregate structure, suppressing the hysteresis effect. Accordingly, the large thermal and conformational hysteresis associated with native PLP chains appears to result from a noninterfering aggregation above the critical temperature.

This study sought to explore the rheological and tribological properties of fucoidan-xanthan gum (XG) mixtures at different fucoidan concentrations. A conformational transition of XG from disordered to ordered forms was observed with an increasing fucoidan concentration, as determined by intrinsic viscosity measurements and Fourier transform infrared analysis. All mixtures exhibited non-Newtonian flow behavior with the yield stress. The mixture sample with 0.5% fucoidan displayed higher apparent viscosity at 100 s^-1, yield stress, and viscoelastic moduli values than XG alone, suggesting viscoelastic synergism between the two biopolymers. However, these values exhibited a decreasing trend with higher fucoidan concentrations (0.5-2.0%), indicating a nullification of synergism. While XG alone exhibited antithixotropic behavior, fucoidan-XG mixtures showed thixotropic behavior, most pronounced at 1.0% fucoidan. A decreasing trend was observed in the maximum friction coefficient as the fucoidan concentration increased, indicating better lubricant properties. Collectively, our findings may enable widespread adoption and application of fucoidan in various industries.

Traumatic brain injury (TBI) activates the NF-κB pathway in microglia and astrocytes, which secrete pro-inflammatory cytokines that disrupt the blood-brain barrier (BBB). Curdlan derivatives are promising carriers for the delivery of siRNA drugs. Herein, we evaluated the glial cell specificity, siRNA delivery efficiency, and the subsequent phenotypic regulation of glial cells by the Curdlan derivatives in the TBI mouse model. Our in vitro and in vivo studies confirmed that the (1) pAVC4 or CuMAN polymer encapsulating siRNA were internalized by astrocytes and microglia in a receptor-dependent manner; (2) systemic administration of the pAVC4 or CuMAN polymer encapsulating siRNA resulted in significant gene silencing efficiency, altered the phenotypic polarization of glial cells, and regulated the secretion of inflammatory cytokines; (3) this lessened neuroinflammation, ameliorated BBB destruction, and improved vascular recovery. These data suggested that pAVC4 and CuMAN polymers are promising RNA delivery vehicles that can efficiently deliver siRNA to the target cells.

One-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimers (IAJDs) were discovered in our laboratories in 2021 to represent a new class of synthetic vectors for the targeted delivery of messenger RNA (mRNA). They coassemble with mRNA by simple injection of their ethanol solution into a pH 4 acetate buffer containing the nucleic acid into monodisperse dendrimersome nanoparticles (DNPs) with predictable dimensions. DNPs are competitive with 4-component lipid nanoparticles (LNPs), which are used in commercial COVID-19 vaccines, except that IAJDs are prepared in fewer reaction steps than each individual component of the LNPs. This simple methodology for the synthesis of IAJDs and their coassembly with mRNA into DNPs, together with the precise placement of their individual components and indefinite stability at room temperature in air, make them attractive candidates for the development of nanomedicine-based targeted mRNA delivery. Access to the large-scale synthesis of IAJDs without the need for sophisticated technologies, instrumentation, and synthetic skills is expected to open numerous new opportunities worldwide in nanomedicine. The goal of this publication is to report an accelerated ten-gram-scale synthesis of IAJD97 from inexpensive food additives obtained from renewable plant phenolic acid starting materials by methodologies accessible to any laboratory. This accelerated synthesis can be accomplished in 4 days. We expect that the work reported here will impact the field of nanomedicine in both developed and less developed countries.

Hepatitis B virions are double-shelled particles, with a diameter of 40-42 nm, consisting of a nucleocapsid called the HBV core protein (HBV Cp). It is an ordered assembly of 90-120 homodimers arranged in an icosahedral symmetry. Both the full-length HBV Cp and the first-149 residue domain, HBV Cp149, can spontaneously assemble in vitro into capsids with 120 Cp dimers (T = 4) or 90 Cp dimers (T = 3), triggered by high ionic strength of 0.25-0.5 M NaCl. The assembly disassembly of HBV Cp149 capsids are generally studied by light scattering, size-exclusion chromatography, atomic force microscopy, transmission electron microscopy, and other high-end expensive techniques. Here, we report a simple, yet robust, label-free technique exploiting protein charge transfer spectra (ProCharTS) to monitor the capsid assembly in real-time. ProCharTS absorption in the near UV-visible region (250-800 nm) arises when photoinduced electron transfer occurs from HOMO of COO^- in glutamate (donor) to LUMO of NH₃⁺ in lysine or polypeptide backbone (acceptor) of the protein. Alternatively, it can also occur from polypeptide backbone (donor) to acceptor in arginine, histidine, or lysine cation. ProCharTS is observed profusely among proximal charge clusters in folded proteins. Here, we show that, ProCharTS absorption among growing HBV capsids is amplified when HBV Cp homodimers assemble, generating new contacts among charged residues in the dimer-dimer interface. We notice a time-dependent sigmoidal increase in ProCharTS absorbance and luminescence during capsid formation in comparison to pure dimers. Additionally, a combined approach of anisotropy-based fluorescence assay is reported, where an increased fluorescence anisotropy was observed in capsids as compared to native and unfolded dimers. We conclude that ProCharTS can serve as a sensitive label-free tool for rapid tracking of capsid assembly in real-time and characterize the assembled capsids from dimers.

Cationic amphipathic antimicrobial agents inspired by antimicrobial peptides (AMPs) have shown potential in combating multidrug-resistant bacteria because of minimal resistance development. Here, this study focuses on the development of novel cationic amphipathic macromolecules in the form of dendrons and polymers with different molecular weights that employ secondary amine piperidine derivative as the cationic moiety. Generally, secondary amine compounds, especially at low molecular weights, have stronger bacteriostatic, bactericidal, and inner membrane disruption abilities than those of their primary amine counterparts. Low molecular weight D2 dendrons with two cationic centers and one hydrophobic dodecyl chain produce outstanding synergistic activity with the antibiotic rifampicin against Escherichia coli, where one-eighth of the standalone dose of D2 dendrons could reduce the concentration of rifampicin required by up to 4000-fold. The low molecular weight compounds are also less toxic and therefore have higher therapeutic index values compared to compounds with larger molecular weights. This study thus reveals key information that may inform the design of future synthetic AMPs and mimics, specifically, the design of low-molecular-weight compounds with secondary amine as the cationic center to achieve high antimicrobial potency and biocompatibility.

Polymer self-assemblies driven by enthalpic interactions, such as hydrogen bonding and electrostatic interactions, exhibit distinct properties compared to those driven by hydrophobic interactions. Carbohydrate-carbohydrate interactions, which are observed in physiological phenomena, also fall under enthalpic interactions. Our group previously reported on self-assemblies of methacrylate-type glycopolymers carrying mannose units in the presence of calcium ions; however, a detailed study of these interactions was lacking. In this work, we investigated the interactions between glycopolymers using the quartz crystal microbalance (QCM) method. Our quantitative analysis revealed that the interactions between the glycopolymers were influenced by the carbohydrate structures in the side chains, the types of divalent metal ions, and the structures of the polymer main chains. Notably, the strongest interaction was observed in the combination of methacrylate-type glycopolymers carrying mannose units and calcium ions, demonstrating their potential as a driving force for polymer self-assembly.