ACS Applied Bio Materials最新文献

This study reports a facile approach for the green synthesis of a high-performance magnetic resonance/computed tomography (MR/CT) dual-modal imaging nanoprobe. The probe, designated as NPs-TCZ, is synthesized via one-step self-assembly of two amphiphilic block copolymers, namely, PEG-DTIPA-TCZ and pal-GGGGHHHHD. The NPs-TCZ exhibits a high longitudinal relaxivity (9.60 mM^-1 s^-1) and X-ray absorption (58.2 Hu mM^-1), as well as excellent water solubility and biocompatibility. The MR/CT dual-modal imaging can synergistically visualize synovial inflammation and bone erosion, which are both important clinical indicators for assessing arthritis severity, enabling sensitive diagnosis and prognostic assessments of rheumatoid arthritis (RA). The active targeting capability of tocilizumab (TCZ) enables the specific accumulation of NPs-TCZ at inflamed joints rather than healthy joints, significantly enhancing the imaging signals and minimizing its potential side effects. In vivo assays using both collagen-induced arthritis mice and acute arthritis mice demonstrate high performance and effectiveness in MR/CT dual-modal imaging of inflamed joints. This study provides insights into not only RA diagnosis in a more accurate manner but also the synthesis of multifunctional nanoprobes in a more robust and mild manner.

A material that was able to simultaneously sense a bacterial presence and to release antimicrobial peptides (AMP) on demand in a tunable amount was developed. Simultaneous sensing and release were achieved by the combination of a bacteria-sensing hydrogel with antimicrobial-peptide-carrying mesoporous silica particles or coatings. The mesoporous silica with a mesopore diameter of 22 nm was functionalized with a covalently grafted green light-sensitive linker, to which antimicrobial peptides were covalently attached. The gelatin-based hydrogel, which contains C14R-functionalized mesoporous silica particles, is designed to respond to bacterial presence as it may occur, e.g., in a wound's microbiological environment. In the presence of bacteria and 0.1% trypsin, a protease enzyme simulating bacterial presence, the hydrogel, deposited in a donut shape, undergoes a shape loss as the bacteria cleave cross-linking bonds within the hydrogel. When observing hydrogel shape loss after 2 h as a readout of a bacterial infection, subsequent irradiation triggers the release of antimicrobial peptides on demand with adjustable concentration-time profiles. The sensing and on-demand release are integrated into commercially available wound dressing fabrics, demonstrating an application proof-of-concept. Characterization using ATR-IR spectroscopy, TGA, and BCA validates the successful fabrication and release. The H1.6P composite released antimicrobial agents, reaching concentrations of up to 298 μg/mL at pH 7.4 from a 300 μL sample. The efficacy of the released C14R against E. coli BL21(DE3) is illustrated. Overall, the multifunctionality of this approach presents a promising step toward on-demand wound care and thus for reducing side effects and antibiotic resistance.

Plant exosomes, small vesicles released by plant cells that contain various bioactive molecules, have garnered great attention for their potential applications in medicine, yet their delivery applications for skincare remain underexploited. Resveratrol (RES), renowned for its remarkable antiaging properties, faces challenges in transdermal absorption due to the stratum corneum barrier, hindering its efficacy. To address this, we developed a delivery system incorporating RES-loaded plant (Leontopodium alpinum) exosome (LEOEXO@RES). Evaluation through both in vitro and in vivo experiments demonstrated LEOEXO@RES's enhanced delivery of bioactive compounds and multifaceted skincare impact. Specifically, this approach not only promoted environmentally responsible waste reuse but also achieved harmonious synergy between LEOEXO carriers and RES, enhancing their overall efficacy. The LEOEXO@RES effectively ameliorated inflammation levels and inhibited cellular senescence, highlighting its promising potential in antiaging skincare applications.

Thrombosis, a common underlying mechanism of myocardial infarction, ischemic stroke, and venous thromboembolism, is the leading cause of death in patients. Owing to their lack of targeting ability, short half-life, low utilization rate, and high risk of bleeding side effects, the current first-line thrombolytic drugs are unable to meet the requirements for effective treatment of thrombi. Photothermal therapy (PTT) represents a promising thrombolytic modality due to its precise spatiotemporal selectivity and minimal invasiveness. However, the efficacy of PTT is constrained by the limited penetration depth of conventional wavelengths, low energy conversion efficiency, and suboptimal performance of photothermal agents. Recent advancements have demonstrated that near-infrared (NIR)-mediated photothermal conversion nanomaterials exhibit significant advantages in treating thrombotic diseases. These NIR-mediated nanomaterials can rapidly convert light energy into heat via the Landau damping effect, achieving deeper tissue penetration without inducing damage, thereby enhancing the effectiveness of photothermal thrombolysis. Moreover, the modifiable nature of these nanomaterials facilitates the targeted aggregation of thrombolytic drugs at the site of thrombosis, enabling specific and effective therapy. In this review, we systematically summarize recent advances in photothermal nanomaterials with potential therapeutic applications for thrombus treatment. Specifically, we focus on composite photothermal nanomaterials that incorporate multiple components in the construction of nanocarriers. We highlight the modification technologies that utilize specific targeting ligands for enhanced thrombus treatment and the application strategies of biomimetic nanomaterials in antithrombotic therapy. Additionally, we discuss combined thrombolytic approaches such as light-triggered nitric oxide release, thrombolytic drug loading, and photodynamic therapy integration. These methods can help mitigate the risk of secondary microvascular embolization, which is crucial for comprehensive thrombus management. Collectively, these strategies offer novel insights into the treatment of thrombotic diseases.

Both silicon (Si) and magnesium (Mg) ions play essential roles in bone health. However, the precise mechanisms by which these two ions enhance osteogenic differentiation remain to be fully elucidated. Herein, a Si-Mg dual-ion system was designed to investigate the effects of Si and Mg ions on the cytological behavior of mouse bone marrow mesenchymal stem cells (mBMSCs). The molecular mechanism of the Si-Mg dual-ion system regulating osteogenic differentiation of mBMSCs was investigated by transcriptome sequencing technology. In the single-ion system, the Si group with concentrations of 1.5 and 0.75 mM exhibited good combined effects (cell proliferation, alkaline phosphatase (ALP) activity, and osteogenic differentiation gene expression (Runx2, OPN, and Col-I)) of mBMSCs. The Mg group with concentrations of 5 and 2.5 mM showed better combined effects (cell proliferation, ALP activity, and osteogenic differentiation gene expression) of mBMSCs. In the dual-ion system, the silicon (0.75 mM)-magnesium (2.5 mM) experimental group significantly enhanced the proliferation, ALP activity, and osteogenesis-related gene expression (Runx2, OPN, and Col-I) of mBMSCs. The analysis of transcriptome sequencing results showed that Mg ions had a certain pro-stem cell osteogenic differentiation regulatory effect. Si ions had a stronger regulation on osteogenic differentiation than the Mg ions. The regulation of osteogenic differentiation by Si-Mg dual ions was synergistically enhanced compared to that of a single ion. In addition, the transforming growth factor beta (TGF-β) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway were involved in mediating the pro-stem cell osteogenic differentiation by Si-Mg dual ions. This study sheds light on investigating the molecular mechanism of dual-ion regulation of the osteogenic differentiation of mBMSCs and enriches the theory of ion-regulating osteogenic differentiation.

DNA-related enzymes are associated with various diseases and have been potential biomarkers for clinical diagnosis. Developing robust and ultrasensitive methods is extremely favorable for the detection of these biomarkers. To this purpose, a primer-regulated rolling circle amplification (RCA) strategy was ingeniously proposed. Briefly, the RCA primer, which was invalidated with 3'-inverted dT (locked state) and unable to initiate an amplification reaction by phi29 DNA polymerase, was embedded with the recognition substrate of the specific enzyme. In the presence of the target, the recognition and cleavage process of the enzyme prompted the release of the 3'-inverted dT and the regeneration of 3'-OH (unlocked state), satisfying the vital prerequisite for RCA. By adopting this programmable and modular design, the recognition substrate can be either single base sites or a specific sequence for different types of enzymes. This also enables us to conduct single or multiple enzyme detection conveniently, relying on a logic-controlled manner including YES, OR, AND, and AND-OR operations. Overall, the proposed strategy is uniquely insightful and provides a universal tool for multiple analyses of diverse DNA-related enzymes.

An overarching limitation of therapeutic biologics is the limited half-life these proteins often exhibit once in circulation. PEGylation, the chemical conjugation of proteins to poly(ethylene glycol) (PEG), is a common strategy to improve protein pharmacokinetics (PK) by enhancing stability, reducing immunogenicity, and decreasing renal clearance. Tissue Inhibitor of Metalloproteinases 2 (TIMP2) is a 22 kDa matrisome protein that exhibits therapeutic potential across a range of human disease models yet possesses a short serum half-life. To advance the therapeutic development of recombinant His-tagged TIMP2 (TIMP2), we utilized primary amine conjugation (1 kDa) and site-specific histidine conjugation (10 kDa) to improve its circulating half-life. Primary amine conjugation of PEG molecules to TIMP2 (TIMP2-a-PEG(_n)) is efficient, yet it produces multiple positional isomers that are difficult to purify. Furthermore, high levels of conjugation can affect the MMP-inhibitory activity of TIMP2. Despite this, TIMP2-a-PEG(_n) displays a significant improvement (11.5-fold) in serum half-life versus unconjugated TIMP2. In contrast, site-specific histidine conjugation targets the histidine tag, enabling the purification of mono-PEGylated (TIMP2-H-PEG₍₁₎) and di-PEGylated (TIMP2-H-PEG₍₂₎) forms. Our findings demonstrate that TIMP2-H-PEG₍₁₎ exhibits improved PK with enhanced stability and a 6.2-fold increase in circulating half-life while maintaining MMP-inhibitory activity. These results suggest that site-specific PEGylation at a C-terminal His₆ tag is a promising approach for further preclinical development of TIMP2 as a therapeutic biologic.

Conventional food preservation techniques often require external devices, increasing costs and posing challenges in maintaining food quality. In this study, we developed blue titanium dioxide-tungsten trioxide-carboxymethyl cellulose (BTO-WO₃-CMC) photocatalyst surfaces integrated onto inert substrates for food preservation. The inclusion of CMC enhanced Z-scheme heterojunction formation, improving visible light absorption, as confirmed by ultraviolet-visible spectra. Sodium silicate (SS) improved adhesion between BTO-WO₃-CMC and the target substrate via hydrogen bonding. Analysis with X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and energy-dispersive X-ray spectroscopy (EDS) confirmed the crystalline integrity of BTO and WO₃ and a consistent coating smoothness. BTO-WO₃-CMC coatings extended the shelf life of strawberries to 14 days under ambient indoor lighting at 600 lx. Optimal preservation was achieved with a 0.01 g, 4 μm thick catalyst coating. Comparative experiments showed BTO-WO₃-CMC's superior efficacy over P25-WO₃-CMC and BTO-CMC. The coating was nontoxic in darkness and minimally reduced cell viability under room light. Antibacterial effects, attributed to reactive oxygen species (ROS) generation, were confirmed against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). This study presents a noninvasive, device-free method to extend food longevity, presenting a promising solution to the food waste challenge.

Resilient hydrogels are of great interest in soft tissue applications, such as soft tissue engineering and wound healing, with their biomimetic mechanical and hydration properties. A critical aspect in designing hydrogels for healthcare is their functionalities to control the surrounding biological environments to optimize the healing process. Herein, we have created an elastomer-clay nanocomposite hydrogel system with biomimetic mechanical behavior and sustained drug delivery of bioactive components and malodorous diamine-controlling properties. These hydrogels were prepared by a combined approach of melt intercalation of poly(ethylene glycol) and montmorillonite clay, followed by in situ cross-linking with a branched poly(glycerol sebacate) prepolymer. The hydration, vapor transmission, and surface wettability of the hydrogels were readily controlled by varying the clay content. Their mechanical properties were also modulated to mimic the Young's moduli (ranging between 12.6 and 105.2 kPa), as well as good flexibility and stretchability of soft tissues. A porous scaffold with interconnected pore structures as well as full and instant shape recovery was fabricated from a selected nanocomposite to demonstrate its potential applications as soft tissue scaffolds and wound healing materials. Biodegradability and biocompatibility were tested in vitro, showing controllable degradation kinetics with clay and no evidence of cytotoxicity. With the high surface area and absorption capacity of the clay, sustained drug delivery of a proangiogenic agent of 17β-estradiol as a model drug and the ability to control the malodorous diamines were both achieved. This elastomer-clay nanocomposite hydrogel system with a three-dimensional interconnected porous scaffold architecture and controllable hydration, mechanical, and biodegradable properties, as well as good biocompatibility and the ability to control the biological chemical species of the surrounding environments, has great potential in soft tissue engineering and wound healing.

Addressing the growing concern about antibiotic-resistant bacteria, we have developed a series of polymers exhibiting intrinsic antibacterial activities with a dual-targeting system that induces physical lysis upon copolymer coalescence with bacterial matter. These polymers are equipped with two orthogonal binding motifs that form electrostatic interactions and dynamic covalent complexes on bacterial surfaces and exhibit potent antibacterial activity against Gram-positive and Gram-negative bacteria. The effect of the chemical composition and architecture of copolymers incorporating phenylboronic acid and quaternary ammonium groups on the antimicrobial activities was systematically examined. This work expands the current chemical repertoire to combat antimicrobial resistance by intrinsically antibacterial polymers with a unique mode of action.