ACS Applied Bio Materials最新文献

Although natural killer (NK) cells are key players in the immune response against tumors, their performance is restricted when it comes to solid cancers like triple-negative breast cancer (TNBC). This study proposes an NK cell-mediated immunotherapy strategy that enhances NK cytotoxicity by modulating the stiffness of TNBC cells through mechanical vibration. Using an in vitro model with MDA-MB-231 cells, a vibration culture system (1.0 g at 50 Hz, 1 min stimulus/1 min rest for 1 h) was applied to increase cell stiffness. Cytotoxicity assays revealed a 2.45-fold increase in NK cell-mediated killing of stiffened MDA-MB-231 cells compared to controls. Immunofluorescence, RT-qPCR, and calcium flux assays demonstrated enhanced NK cell activation, including improved target recognition, mechanosensitive ion channel activation, calcium influx, lytic granule release, and cytokine responses. These findings suggest that mechanical vibration-induced tumor cell stiffening is a promising, noninvasive strategy to improve NK cell function and enhance tumor immunotherapy.

This study proposes quaternized lignin (QL) as a sustainable and multifunctional additive for active food packaging applications and presents the development of fish gelatin (FG)-based nanofiber packaging materials. Cationic QL was synthesized via glycidyltrimethylammonium chloride (GTMAC) modification of kraft lignin to enhance its water dispersibility and antimicrobial properties. The resulting QL derivatives were incorporated into FG-based nanofibers via electrospinning, which were stabilized through Maillard reaction-induced cross-linking. The quaternization degree and incorporation of QL into FG nanofibers considerably affected the nanofiber morphology, mechanical properties, hydrophilicity, and structural stability. Antioxidant and antibacterial assays revealed that FG-based QL (FG/QL) nanofibers, especially those containing highly quaternized lignin (QL3), exhibited enhanced radical scavenging and bactericidal activities againstStaphylococcus aureus and Escherichia coli, which were attributed to the synergistic effect of QL and Maillard reaction products. The blueberry preservation test confirmed the practical efficacy of Maillard reaction-cross-linked FG/QL3 nanofibers in extending shelf life by inhibiting microbial spoilage. These results indicated that QL-functionalized FG nanofibers have potential applicability as biodegradable natural materials for active food packaging systems.

With coronary artery disease remaining the leading cause of mortality worldwide, the design and manufacture of clinically viable synthetic coronary artery grafts remains a fundamental healthcare challenge. It is widely accepted that vascular mimicking materials (VMMs) should emulate the heterogeneous biomechanical and biological functions of the multilayered artery wall to ensure long-term patency postimplantation. However, few VMMs can adequately meet these complex design requirements. Poly(vinyl alcohol) (PVA)/gelatin cryogels are prospective VMMs due to their combined mechanical (PVA) and biointegrative (gelatin) features, but their development thus far has been limited to homogeneous constructs. The aim of this research is to assess the mechanical response of biomimetically designed multilayered grafts, simulated using Finite Element Analysis. The impact of a sinusoidal interface on circumferential stress distribution and graft compliance, was explored. Using qualitative insight from research on hydrogel based functionally graded biomaterials, and in the context of subzero extrusion additive manufacturing, rough (infinite) friction was used to model the contact between the layer. It was found that transmural stress patterns were continuously graded (phased) as a function of interface amplitude and frequency. In contrast to laminated models, which displayed a discontinuity in transmural stress between layers. This design methodology illustrates a novel approach to achieving functionally graded synthetic grafts through interface design.

Mitochondria have emerged as critical therapeutic targets in anticancer strategies, particularly for overcoming the inherent resistance challenges during tumor treatment. Herein, we present a metallodrug delivery system (FT-lipoAu/PTX) with multistage targeting capability, designed to achieve mitochondria-specific photothermal apoptosis and reverse tumor chemoresistance. FT-lipoAu/PTX was composed of folic acid (FA) and triphenylphosphonium (TPP)-modified paclitaxel (PTX) liposomes encapsulating gold nanorods (AuNRs). FA and TPP dual modification enable multistage targeting of folate receptor-overexpressing breast tumor cells, facilitating FT-lipoAu/PTX accumulation in mitochondria. Under near-infrared (NIR) laser irradiation, FT-lipoAu/PTX generated localized hyperthermia, triggering mitochondrial membrane potential depolarization, cytochrome c release, reduced cellular metabolic efficiency, and suppressed ATP synthesis. Importantly, this tumor metabolic reprogramming process significantly downregulated drug-resistance protein expression [e.g., efflux pump P-glycoprotein (P-gp)], thereby increasing intracellular PTX retention and enhancing chemotherapeutic efficacy. In a chemoresistant breast tumor murine model, FT-lipoAu/PTX demonstrated prolonged circulation, high tumor specificity, potent tumor growth suppression, and minimal systemic toxicity. Collectively, FT-lipoAu/PTX leveraged mitochondria-targeted phototherapy to overcome chemoresistance barriers, providing a robust strategy for effective chemotherapy.

RNA interference (RNAi)-based biopesticides offer precise pest control with minimal environmental impact, yet their field efficacy is limited by rapid degradation of double-stranded RNA (dsRNA) due to UV exposure, nucleases, and poor foliar adhesion. To address these challenges, we developed a mineral oil-based water-in-oil (W/O) emulsion to encapsulate dsRNA targeting the Amphitetranychus viennensis V-ATPase A gene. The formulation was optimized through hydrophilic–lipophilic balance (HLB) screening (optimal HLB = 10), ternary phase ratio adjustment (oil:water:surfactant = 64:20:16), and dsRNA loading concentration tests (optimal: 5000 mg/L). Bioassays assessed toxicity against eggs, nymphs, and adults of Amphitetranychus viennensis, alongside field trials comparing dsRNA@W/O (750× dilution) with naked dsRNA, double-applied naked dsRNA, and the chemical control etoxazole. Key findings demonstrated that dsRNA@W/O significantly enhanced stability: after 72 h of UV/air exposure, 93.67% of activity was retained, compared to complete degradation of naked dsRNA. The formulation accelerated lethality, reducing median lethal time (LT₅₀) from 4.84 to 1.95 days for nymphs and from 4.82 to 2.65 days for adults. Field efficacy at 20 days post-treatment reached 85.75% at 1.33 mg/L dsRNA, outperforming naked dsRNA (62.79%) and approaching etoxazole (95.69%), while using one-third the active ingredient of conventional dsRNA treatments. This work demonstrates a cost-effective, scalable mineral oil encapsulation strategy that synergizes RNAi-mediated pest control with mineral oil’s physical effects, offering a sustainable, environmentally safe, and economically feasible pest management approach.

Many gastropods secrete mucus, which is more viscous and adhesive than the common trail mucus. The primary biochemical distinction between the two types of mucus is the higher protein content of the adhesive mucus. Not enough is known about the function of each of these proteins. In the current study, two of such mucus proteins were isolated from the adhesive mucus of the land snail Macrochlamys indica. In an attempt to imitate the structure of the mucus, these proteins were mixed with commercial hyaluronic acid (HA). The resultant hydrogel was found to have adhesive properties. A cell viability assay revealed that each of the hydrogel components and their mixtures were biologically safe and compatible. The in vitro cell migration assay showed better wound closure in case of the mucus protein as compared to HA, which is already known for its wound healing properties. The hydrogel was used for incision wound healing in mice, followed by histological staining. The result showed faster healing when compared to that of commercial wound healing ointment. In conclusion, this study presents a wound repair material, formulated from snail protein and HA and useful as an adhesive wound dressing with healing effects.

The enzymatic degradation of hyaluronic acid (HA) and carboxyl-modified chitosan (CC) polymers in aqueous dispersions can be controlled by dynamic covalent cross-linking. Unlike un-cross-linked HA, dynamic covalent cross-linking preserves the viscoelastic behavior of HA dispersions when exposed to hyaluronidase enzyme. Among the dynamic covalent cross-linked CC dispersions, only dispersions with degrees of deacetylation of 98% (CC98) partially upheld the viscoelastic behavior under lysozyme-mediated degradation. Overall, our results suggest that dynamic covalent cross-linking can produce injectable HA and CC dispersions with partial enzymatic degradation resistance.

Exosomes are nanoscale extracellular vesicles secreted by cells that possess molecular and pathological characteristics of their cellular origin. Acting as natural carriers, they efficiently transport a diverse cargo of biomolecules, including proteins, nucleic acids, lipids, metabolites, and small molecules facilitating highly specific intercellular communication. Owing to their inherent biocompatibility, target specificity, and cargo versatility, exosomes have emerged as one of the most promising platforms for diagnostic and therapeutic applications. This review comprehensively elaborates on intricate biogenesis and regulatory pathways governing exosome production, examines their structural composition and cargo loading preferences, and highlights emerging strategies to enhance their functional capabilities. We further explore recent breakthroughs at the intersection of exosome biology and nanotechnology, emphasizing their roles in maintaining cellular homeostasis, advancing disease diagnostics, and enabling targeted therapeutic delivery. Finally, we critically address current challenges and limitations in exosome research, offering insights into innovative solutions and future directions for their clinical translation.

Antibacterial resistance has become a growing global health challenge, with multidrug-resistant pathogens posing significant threats to public health. Traditional antibacterial agents often encounter problems such as high costs, low efficiency, poor antibacterial efficacy, and restricted biocompatibility. Thus, there is an urgent need to develop materials with enhanced antibacterial properties. In this study, CaCO₃/C/PDA antibacterial composite was designed as a high-efficacy antibacterial agent against Gram-negative bacteria. Under near-infrared light irradiation (808 nm, 0.3 W/cm², 4 min), the CaCO₃/C/PDA^0.2 exhibited satisfactory antibacterial activity against Gram-negative bacteria, including Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia, with sterilization rates of 91.7%, 98%, and 100%, respectively. The antibacterial mechanism could be attributed to the synergistic effects of photothermal and photodynamic therapy, where high temperatures can denature bacterial proteins and reactive oxygen species (ROS) may disrupt bacterial metabolism, ultimately leading to bacterial death. All of the experimental results confirmed that CaCO₃/C/PDA is a promising antimicrobial agent for Gram-negative bacterial infections. In addition, the in vitro toxicity tests also confirmed that CaCO₃/C/PDA possessed excellent biocompatibility. Overall, this work offers an approach and strategy for the development of next-generation antimicrobial materials with broad biomedical potential.

Mucosal barriers protect epithelial tissues but limit the diffusion of therapeutic nanoparticles, posing a major challenge for transmucosal drug delivery. Surface chemistry plays a key role in navigating this barrier, where both mucoadhesive and mucopenetrating strategies have shown value. In this study, we demonstrate how combining zwitterionic and boronic acid functionalities enables the rational design of nanoparticles with tunable interactions toward mucus. Block copolymers of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly(carboxybetaine) (PMCB), with or without a terminal aminophenylboronic acid (APBA), were synthesized and used as nanoparticle stabilizers via flash nanoprecipitation using a multi-inlet vortex mixer. Nanoparticle permeation was examined in purified sheep small intestine mucus. PMPC-based nanoparticles exhibited superior transport compared to PMCB- and PEG-containing analogs. Increasing APBA density led to reduced permeation due to specific interactions with mucin-associated sialic acids; this effect was reversed upon preincubation with free sialic acid. Zeta potential analysis before and after mucus exposure confirmed preserved surface integrity regardless of APBA density. These findings highlight the ability to balance mucoadhesive and mucopenetrating properties via surface chemistry, offering a flexible platform for engineering nanoparticles optimized for mucus barrier traversal and downstream targeting in transmucosal drug delivery.