Biomacromolecules最新文献

Molecular crowding─a defining feature of the cellular environment─affects folding kinetics, conformation, and stability of G-quadruplex (GQ) structures. However, its influence on the overall architecture and accessibility of telomeric overhangs containing multiple GQs remains largely unexplored. In this study, we employed single-molecule FRET and FRET-PAINT to address this question. We examined the accessibility of telomeric overhangs, capable of forming 1-6 GQs, to a short complementary peptide nucleic acid (PNA) imager probe in the presence of 200 and 6000 Da polyethylene glycol (PEG) molecules (PEG-200 and PEG-6000). We observed a progressive compaction and architectural condensation of the overhang as PEG concentration increased. At 30% concentration, this compaction was accompanied by approximately 3-fold and 8-fold reduction in probe accessibility in PEG-200 and PEG-6000, respectively. These findings offer new insights into how the crowded cellular environment may compact telomeric overhangs and modulate their structural and functional properties.

Paramylon acetate and cellulose acetate with different degrees and distributions of substituents were synthesized by two different methods, de-esterification from triesters with NaOH treatment and direct esterification. Paramylon and cellulose acetate obtained by de-esterification exhibited a lower degree of substitution (DS) at C6 and a higher DS at C2 position. All of the acetate samples with different DSs were thermoformable, producing transparent films. However, melt-pressed films obtained through de-esterification exhibited greater flexibility than those prepared via direct esterification. Simultaneously, biochemical oxygen demand (BOD) tests demonstrated that paramylon and cellulose acetate obtained by de-esterification show higher biodegradability than esterification ones with the same DS. This increased biodegradability may be attributed to the lower DS of the acetyl group on C6 for paramylon and cellulose acetate obtained by de-esterification. De-esterification with NaOH treatment was validated as an effective approach for producing polysaccharide esters with excellent mechanical properties and biodegradability for both paramylon and cellulose.

The growing demand for biodegradable polymers capable of stimuli-responsive drug release is challenged by limitations in facile synthetic methods. In this study, two biotin-functionalized amphiphilic polyesters (P1 and P2) were synthesized through step-growth polymerization, aiming to achieve biotin receptor-mediated cancer cell selective uptake. In addition to polar biotin, P2 incorporates a hydrophobic fluorescent dye, which enabled intracellular fluorescence tracking. P2 self-assembled into highly biocompatible spherical nanoaggregates (∼120 nm) in water, which showed effective encapsulation of the hydrophobic anticancer drug doxorubicin (DOX). It displayed ∼85-90% internalization in biotin-overexpressed cancer cells (HeLa and MCF7) contrary to only ∼5-10% uptake in noncancerous cells (NIH 3T3), as determined by flow cytometry and fluorescence microscopy. Cell-selective DOX release was likely induced by the polyester degradation in the acidic cancer microenvironment and via endogenous esterases, evident from size exclusion chromatography (SEC) and dynamic light scattering (DLS) experiments. These findings highlight the potential of stimuli-responsive degradable polyester nanocarriers for targeted cancer treatment.

Lignin from birch (BLN), spruce (SLN), and wheat straw (WSLN) was first converted into bromoisobutyrate-based macroinitiators (LNBr) and subsequently grafted with n-butyl acrylate (LNBA) copolymers via atom transfer radical polymerization (ATRP). The influence of hardwood, softwood, and straw lignin on the properties of the copolymers was investigated in terms of thermal behavior, rheology, and tack test. Structural analysis by FTIR, NMR, and SEC/GPC confirmed successful grafting and an increased and broad molecular weight distribution. Thermal analysis (DSC and TGA) showed increased glass transition temperatures (T_g) and different thermal degradation compared to the homopolymer poly(n-butyl acrylate). Additionally, BLN-based copolymers with varying degrees of polymerization (2, 4, and 10) were synthesized to optimize the material properties. The copolymers showed adhesive properties for all BLNBA and SLNBA variants, with BLNBA2 and BLNBA4 meeting the Dahlquist criteria for pressure-sensitive adhesives.

Polysulfoniums, sulfur-rich cationic polymers with trivalent sulfonium motifs, are promising biomaterials due to their high charge density, structural flexibility, and biocompatibility. This review highlights recent synthetic strategies: main-chain polymers via thiol-ene/epoxy click chemistry and pendant functionalization using ROMP, ROP, or RAFT polymerization, alongside postpolymerization alkylation. Their sulfonium groups selectively disrupt anionic microbial membranes, enabling broad-spectrum antibacterial action against pathogens like MRSA without inducing resistance. Stimuli-triggered dissociation enhances intracellular delivery, bolstering efficacy while reducing toxicity. These polymers also stabilize protein via sulfonium-π interactions and enable targeted therapies though zwitterionic or covalent architectures. The tunable UCST/LCST behavior and anion/pH responsiveness support smart hydrogels for wound healing and biofilm removal. Compared to ammonium and phosphonium analogs, polysulfoniums offer superior biocompatibility and membrane disruption, making them ideal for antimicrobial coatings, gene therapy, and cancer treatment. This interdisciplinary synergy between polymer science and biotechnology underscores their potential to address critical challenges in healthcare and materials science.

Programmed death-ligand 1 (PD-L1), an immune checkpoint protein, serves as a "don't eat me" signal that allows cancer cells to evade detection and clearance by the immune system. Blocking PD-L1 with the PD-L1 antibody (aPD-L1) can restore the immunity. Photothermal therapy (PTT), meanwhile, induces local tumor cell death and releases damage-associated molecular patterns (DAMPs) to further stimulate immune responses. Here, we developed a multifunctional nanogel system, composed of β-cyclodextrin (β-CD), polyethylenimine (PEI), and polyethylene glycol (PEG), referred to as CPP nanogels, designed for the codelivery of aPD-L1 and indocyanine green (ICG), a PTT photosensitizer. The β-CD moieties facilitated ICG loading through host-guest interactions, while PEI enabled aPD-L1 conjugation. Upon targeting tumor cells, the nanogels blocked PD-L1 and, under 808 nm laser irradiation, triggered PTT-induced DAMPs release. By promoting both heat-induced cell death and immune responses, the multifunctional CPP nanogels represent a promising system potentially for treating localized and metastatic cancers.

Respiratory viruses, such as influenza A virus and SARS-CoV-2, continue to pose significant global health challenges. Current antivirals, which are often specific to a single virus, face limitations due to rapid mutations and the emergence of new strains. In this study, we introduce styrene maleic acid copolymer lipid particle nanodiscs (SMALP-NDs) as a broad-spectrum antiviral platform that employs a dual mode of action. First, SMALP-NDs bind to positively charged viral proteins via their negatively charged surfaces, thereby blocking viral entry. Second, they induce the collapse of viral envelopes under acidic conditions similar to those in the endosome, leading to virus inactivation via a cell-mediated mechanism. SMALP-NDs demonstrated broad-spectrum antiviral activity against influenza A/B and multiple SARS-CoV-2 variants, including Omicron JN.1, as well as herpes simplex virus types 1 and 2 and vaccinia virus, underscoring their versatility. Intranasal administration of SMALP-NDs has successfully protected mice from lethal H1N1 and H5N2 influenza A viruses as well as SARS-CoV-2. These findings underscore that SMALP-NDs effectively counteract the increasing positive charge of emerging viral proteins through their negatively charged surfaces while leveraging pH-responsive virus inactivation mechanisms to achieve high antiviral efficacy with low toxicity, offering a significant advantage over traditional antiviral nanomaterials.

Upon the scalable utilization of polyphenols, the design of their composites with polymers has received a great deal of attention. However, the starch polymer has a weak loading of hydrophobic polyphenols typically through noncovalent interactions without biochemical catalysts. Here, we tailor a reticular starch nanostructure from a starch nanosphere precursor (preSNS) that traps ferulic acid (FA) via esterification. The preSNS-FA network is activated by a green physical method via dynamic high-pressure microfluidization, exhibiting an exceptionally higher content of FA (∼38.0%) compared with the conventional starch group (only ∼1.5%). SEM, FTIR, XRD, 13C NMR, 1H NMR, and XPS results as well as molecular dynamics simulation comprehensively confirm the changes in architecture and hydrogen bonding modes with the formation of -COOR-. The preSNS-FA network also has an enzymatic hydrolysis resistance (up to 83.8%). Collectively, this work establishes a high-performance and catalyst-free synthetic route toward an esterified polyphenol complex network with potential applications in nutrient delivery, food packaging, and agriculture fields.

Sinomenine hydrochloride (SH) has been clinically utilized for many years to treat rheumatoid arthritis (RA) in both oral and injectable forms. However, its low bioavailability, poor targeting, high dosage requirements, and side effects, present significant challenges. This study developed folic acid-carboxymethyl chitosan-modified sinomenine-curcumin nanopolymers (named SCNP) for the targeted treatment of RA, to reduce dosage and side effects. The design of SCNP employs folic acid (FA) as a targeting moiety, facilitating specific binding to the folate receptor (FR) on the surface of macrophages and enabling internalization into activated macrophages via endocytosis, thereby achieving targeted delivery to sites of inflammation. In a rat and cell model of RA, SCNP was found to decrease reactive oxygen species (ROS) and pro-inflammatory factors while increasing the anti-inflammatory factor IL-10 through the NF-κB/NLRP3 pathway. These findings indicate that SCNP has the potential to lower drug dosage, enhance therapeutic efficacy, and minimize side effects such as diarrhea and rash, thereby highlighting its promise as an inflammation-targeting nanopolymer.

Tumor microenvironment (TME) alteration can lead to tumorigenesis, where tumors evade the immune system and spread. Thus, immunomodulation inside the TME may be a useful therapeutic approach. In this regard, bioprinting has become a potential technique for developing therapeutic solutions that offer improved control over immune modulation. Through the use of novel immune cell therapies and realistic tumor models, it provides a platform for advancing cancer immunotherapy. By examining the complex mechanisms of immunomodulation in tumorigenesis, this review article clarifies how interactions between the immune system and the tumor microenvironment affect the initiation and spread of cancer. Additionally, the effectiveness of 3D bioprinting in modulating and activating immune cells, such as T cells, dendritic cells, and macrophages, has also been analyzed. A summary of current research shows the pivotal role of 3D bioprinting in establishing a solid foundation for advancing anticancer studies and revolutionizing cancer treatment through immunotherapeutic strategies.