Biomacromolecules最新文献

We demonstrate triblock polyelectrolyte complex (PEC) hydrogels as a model platform for protein delivery and unveil their precisely tunable swelling behaviors. PEC hydrogels self-assemble in water, do not require UV light or organic solvents, and demonstrate easily tunable shear properties. However, for PEC hydrogels to be effectively designed as protein delivery vehicles, it is imperative to understand the influence of protein additives on their microstructure and swelling behavior. Herein, we utilize small-angle X-ray scattering to demonstrate that model proteins, including bovine serum albumin, lipase, human carbonic anhydrase II, and urease, do not perturb the PEC hydrogel microstructure at therapeutically relevant concentrations. The swelling and dissolution characteristics are shown to be precisely controlled by triblock polyelectrolyte (tbPE) end-block length and concentration. Moreover, we demonstrate that PEC hydrogel swelling and dissolution characteristics, as well as their shear moduli, are unaffected by protein inclusion. Finally, we demonstrate tunable protein release in PEC hydrogels by varying tbPE concentration and end-block length, mixing tbPEs of different lengths to create mixed PEC hydrogels, and incorporating a covalent interpenetrated network. Our work provides easily accessible design parameters to achieve the desired protein release characteristics in PEC hydrogels. At the same time, it also provides insights into the influence of charged macromolecules on the microstructure and dynamics of PEC-based self-assemblies.

Organic luminescent materials are essential for OLEDs and bioimaging, yet traditional π-conjugated molecules face synthetic and environmental challenges. Nonconventional luminescent materials (NLMs) offer better biocompatibility but typically exhibit weak clustering-triggered emission (CTE) in dilute solutions, limiting their biomedical utility. To address this, we synthesized four aspartic acid-based NLMs (S1-S4) featuring hydrophobic segments. These polymers self-assemble into nanoclusters in dilute solutions, restricting molecular motion to enable potent CTE. Remarkably, S1-S4 achieved high photoluminescence quantum yields (up to 10.07% at 0.5 mg/mL) and demonstrated low cytotoxicity. These NLMs function as effective lipid droplet (LD) imaging agents; specifically, S4 exhibited a 94% colocalization rate with the commercial probe Nile Red. By achieving performance comparable to traditional fluorescent probes in dilute states, these NLMs provide a robust, sustainable tool for specific subcellular imaging and advance the practical application of nonconjugated emitters.

Clinical studies have demonstrated that the daily intake of folic acid can reduce the incidence of neural tube defects (NTDs) by 70%. Despite widespread awareness of the need for folic acid supplementation, certain communities remain at a high risk for NTDs. To overcome these limitations, sustained and controlled delivery systems based on natural and synthetic polymers have been extensively explored. However, these systems often fail to maintain long-term release due to an incomplete understanding of how polymer properties influence drug release kinetics. As a result, achieving long-term control of drug release often requires complex strategies, including polymer blending or coating techniques, complicating both device fabrication and the understanding of release mechanisms. In this work, we present a simple yet effective drug delivery system based on modular peptide-like polyesters, specifically designed for tunable, long-term release of folic acid. The well-defined architecture of these systems allows us to clearly demonstrate, through extensive characterization and simulations, that folic acid release is primarily governed by physical and chemical interactions among key functional groups of the polymer, folic acid, and water.

Chaotropes are long known to destabilize protein assemblies and folding. We report that a boron cluster ion, as a weakly coordinating superchaotrope, can paradoxically stabilize protein folding even under extended thermal stresses while broadly inhibiting specific and nonspecific protein-protein interactions at millimolar concentrations for multiple proteins. Thermodynamic and kinetic investigations suggest that the boron cluster ion reduced the association rates of protein association and rendered protein-associative interactions entropically unfavorable. The preliminary utility of this phenomenon is demonstrated by the preservation of protein functions within complex mixtures stored in ambient, uncontrolled conditions, boosting their shelf life and stability against aggregation.

Natural polysaccharides, such as chitosan, offer promising avenues for drug delivery due to their cytocompatibility and ability to interact with cell surfaces. However, the endothelial glycocalyx, a glycan-rich extracellular matrix, presents a barrier that must be navigated for effective intracellular delivery. This study investigates how cationic poly(glucosamine)-based polymers, functionalized with guanidinium or ammonium groups, interact with key glycocalyx components including hyaluronan (HA) and heparan sulfate (HS). We demonstrate that these cationic polymers form tunable biomolecular condensates with glycans, with stronger binding observed for sulfated glycans, HS and heparin, than unsulfated HA. Derivatized chitosan polymers with varied cationic side chains exhibit differential binding affinities and cellular association, with guanidinium-containing polymers showing enhanced interaction with endothelial cells expressing a mature glycocalyx. Quartz crystal microbalance with dissipation monitoring revealed reversible binding profiles influenced by ionic strength, and competitive displacement assays using condensates confirmed preferential binding to heparin over HA. Enzymatic degradation of the glycocalyx reduced polymer-cell association, underscoring the role of the glycans in facilitating the cellular uptake of these polymers. These findings elucidate the mechanisms by which cationic polymers traverse the glycocalyx and highlight the potential of considering the glycocalyx in the design of polymer systems for targeted drug delivery applications.

Evaluating the biomedical potential of marine biopolymers is a promising strategy for their high-value application. This study investigated the ability of collagen derived from Chondrosia reniformis to support cell proliferation and chondrogenic differentiation, assessing its suitability for tissue regeneration. Collagen was isolated, preserving its fibrillar structure and glycosylation features, then cross-linked with EDC, genipin, or glutaraldehyde to produce freeze-dried scaffolds. The resulting structures were characterized in terms of physicochemical properties, morphology, degradation, rheology, and cytocompatibility. While all scaffolds showed comparable degradation and rheological behavior, genipin-cross-linked scaffolds exhibited larger pore sizes, whereas glutaraldehyde-cross-linked scaffolds showed higher water uptake. In vitro assays using ATDC5, BJ, and EA.hy926 cell lines demonstrated superior metabolic activity and proliferation on genipin-cross-linked scaffolds. Additionally, human adipose stem cells displayed early chondrogenic differentiation, evidenced by SOX9, ACAN, and COMP expression under basal conditions. These findings highlight the versatility of C. reniformis collagen for biomedical applications, particularly cartilage regeneration.

Cellulose dissolution remains a fundamental challenge due to its recalcitrant crystalline structure, governed by interchain hydrogen bonds and dispersion interactions. Hydroxide-based systems are industrially relevant but require energy-intensive subzero temperatures. This study employs molecular dynamics simulations to elucidate the molecular mechanisms underlying the dissolution performance of benzyltrimethylammonium hydroxide (BzMe₃NOH) and NaOH. Na⁺ binds to cellulose primarily through electrostatic interactions, whereas the amphiphilic benzyltrimethylammonium cation (BzMe₃N⁺) engages predominantly via vdW interactions, accumulating along the hydrophobic backbone. Both systems exhibit anion-cellulose interactions with hydroxide ions, forming bifurcated hydrogen bonds that facilitate transient deprotonation of hydroxyl groups. A key thermodynamic advantage of BzMe₃N⁺ is that each cation displaces more water molecules away from cellulose's solvation shell than Na⁺ does, reducing the entropic penalty of dissolution. This work establishes that effective dissolution in hydroxide systems requires a synergistic combination of anion-driven hydrogen-bonding disruption and cation-driven dispersion compensation.

This work explores the relationship between the thickness of the shell of polydopamine (PDA) nanocapsules, their protein adsorption, and subsequent cellular uptake. Increasing the polymerization time of dopamine from 3 to 144 h (PCF3-PCF144) on a fructose-curcumin (CCM) template increased the capsule size from 106 to 134 nm, as measured by electron microscopy. XPS analysis revealed slight changes in the surface composition following prolonged dopamine deposition. Analysis of the protein corona using fluorescent techniques and liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that the PDA nanocapsule obtained at the shortest polymerization time (PCF3) adsorbed the most proteins and had the greatest variety, with globin and albumin being abundant. PCF3 also exhibited the highest cellular uptake in three cell lines─the breast cancer cell line MCF-7, bovine aorta endothelial cells, and the macrophage cell line RAW 264.7─while thicker shells resulted in decreased uptake. This work emphasizes that the protein corona can confer colloidal stability in serum and enhance cellular uptake.

Self-assembled proteins can significantly inhibit ice recrystallization, offering potential for cryoprotection. Here, soybean protein amyloid fibrils (SAFs) were fabricated via combined germination and acid-heat-induced fibrillation. Germination enhanced the fibrillation efficiency of soybean protein isolate (SPI). SAFs with the strongest ice recrystallization inhibition (IRI) activity were prepared from SPI of two-day germinated soybeans after 20 h of acidic-heat treatment (SAF-20). SAF-20 exhibited concentration-dependent IRI activity, with stronger inhibition of ice crystal growth at higher concentrations. It showed high ice-affinity adsorption and ice nucleation activity without altering ice crystal morphology. Structural analyses revealed that self-assembly promoted protein aggregation and increased surface hydrophobicity and β-sheet content. These changes strengthened hydrogen bonding at the ice-water interface, forming ordered interfacial water layers that disrupted long-range water ordering and inhibited ice crystal growth. Furthermore, SAF-20 significantly improved post-thaw recovery of cryopreserved Caco-2 cells, demonstrating its cryoprotective efficacy.