ACS Applied Bio Materials最新文献

Sulfur dioxide is one of the gaseous signaling molecules involved in many physiological and pathological processes of living cells, and label-free monitoring of the release of SO₂ on the cell surface provides a facile way to investigate the related cellular processes. Toward this goal, here we engineer a hairpin-containing i-motif (iM-Hp) DNA that effectively binds a benzothiazole-based SO₂-responsive fluorescent probe (PSMB) and remarkably promotes its fluorescence emission. When this light-up system is incubated with SO₂ in aqueous solution, the addition of HSO₃^– to the C═C bond of PSMB destroys the fluorophore structure, accompanied by a sharp decrease in the fluorescence intensity. In this way, SO₂ can be sensitively detected with a high specificity. Based on it, we further construct a cell membrane-anchored SO₂ fluorescent sensor for label-free monitoring the release of SO₂ from HeLa cells stimulated by lipopolysaccharide (LPS), a well-known inducer for cell inflammation. It shows that the level of SO₂ exocytosis increases gradually within 4 h after incubation with LPS, whereas the cell viability almost remains unchanged during this period. This finding discloses a postdrug progressive process of inflammatory cells, highlighting the significant potential of our designed light-up system in monitoring drug-induced early cell lesion.

Nanosized carriers based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) are a versatile delivery system for various therapeutic agents such as anti-inflammatory drugs and plasmid DNA, as well as targeted antitumor drugs and proteins. Earlier, we developed Amph-PVP-based nanoparticles decorated by a modified DR5-specific TRAIL variant DR5-B (PVP-DR5-B) or containing the proteasomal inhibitor bortezomib (PVP-BTZ). Both DR5-B and BTZ have antitumor properties and, when combined, act synergistically on tumor cells. In the present study, Amph-PVP nanoparticles were loaded with BTZ and subsequently decorated with the TRAIL variant DR5-B, producing a dual polymeric bionanocomposite system PVP-BTZ-DR5-B. Using 2D and 3D in vitro cultures of human glioblastoma cell lines U87MG and T98G, it was demonstrated that PVP-BTZ-DR5-B nanoparticles were internalized and accumulated in cells more efficiently, demonstrating significantly enhanced cytotoxicity compared to free DR5-B or PVP-BTZ nanoparticles loaded with bortezomib alone. PVP-BTZ-DR5-B nanoparticles also penetrated the blood–brain barrier more efficiently than DR5-B in an in vitro model. Finally, the enhanced antitumor effect of PVP-BTZ-DR5-B was demonstrated in a xenograft model of U87MG glioblastoma cells in zebrafish embryos in vivo. Thereby, coloading of BTZ and DR5-B into the Amph-PVP nanoparticles is a promising approach to enhance the antitumor efficacy of free drugs and overcome glioblastoma resistance.

Atopic dermatitis (AD) and diabetic wounds are chronic inflammatory skin conditions with limited treatment options. This study investigates the therapeutic potential of sprayable colloidal suspensions composed of cellulose and mannan nanocrystals (CNC/MN) derived from ivory nuts in preclinical models of AD and diabetic wound healing. AD was induced in BALB/c mice using 2,4-dinitrochlorobenzene (DNCB), while diabetes was induced in Swiss mice via streptozotocin before dorsal wounds were created. AD severity was assessed through clinical scoring, scratching behavior, histopathology, oxidative stress markers, inflammatory profiling, and emotional domain evaluation. Wound closure rates, bacterial burden, and histological analysis were used to evaluate diabetic wound healing. CNC/MN-based suspensions alleviated DNCB-induced inflammatory skin damage (back: around 48%, and dorsal skin: around 78%) and reversed depressive-like behavior (around 50%) without affecting locomotor activity. The formulation with higher MN content showed superior efficacy in reducing erythema, edema, and neutrophilic infiltration while restoring antioxidant enzyme activity. In diabetic wounds, suspensions with lower MN or without MN content exhibited the best results, enhancing wound closure, collagen deposition, and reducing inflammation. The CNC/MN-based suspension with lower MN content significantly reduced bacterial colonization in the wound site (around 23%). These findings demonstrate that CNC/MN colloidal suspensions are promising sprayable biomaterials for treating inflammatory skin disorders, mitigating cutaneous and neuropsychiatric AD symptoms while promoting tissue regeneration in diabetic wounds. This study highlights their dual therapeutic potential and sustainable origin, offering an innovative treatment alternative for chronic skin disease.

Small-diameter vascular grafts (SDVGs) have great potential in the treatment of cardiovascular diseases. However, thrombosis and restenosis of SDVGs, caused by incomplete endothelium and abnormal smooth muscle cell proliferation, limit their clinical applications. Hydrogen sulfide (H₂S) is a crucial signaling molecule in the cardiovascular system, playing a vital role in physiological processes such as blood pressure regulation, angiogenesis, and the reduction of vascular hyperplasia, as well as exerting anti-inflammatory effects. In this study, a human hair keratin-based H₂S donor was synthesized and coelectrospun with poly(ε-caprolactone) to develop an H₂S-releasing vascular graft. The graft effectively promoted the growth and migration of HUVECs and suppressed the proliferation of HUASMCs by releasing H₂S. Interestingly, the grafts accelerated endothelium formation under shear stress and protected them from oxidative stress. In vivo experiment also demonstrated that the endothelial layer regenerated without detectable thickening of the smooth muscle layer after 1 month of implantation, which was attributed to the H₂S-mediated effect. Taken together, this study provided strategies for the tissue remolding of small-diameter vascular grafts.

The long-term survival of allografts is primarily compromised by immune rejection, in which M1 macrophage-mediated tissue damage and effector T cell infiltration have been identified as major contributors. Current clinical immunosuppressive drugs face critical limitations, as they either fail to coordinately regulate these two immune cell populations or induce systemic infections and metabolic disorders. To address this challenge, we developed an aminooxyacetic acid (AOAA)-loaded hydrogel delivery system (AOAA-Gel) based on covalently cross-linked oxidized sodium alginate/carboxymethyl chitosan (OSA/CMCS). This hydrogel enables localized and sustained AOAA release, while avoiding systemic toxicity. Mechanistically, AOAA-Gel coordinately modulates the M1/M2 macrophage ratio while expanding regulatory T cells at the graft site, resulting in effective suppression of both effector T cell infiltration and chronic rejection. In a murine allogeneic skin transplantation model, AOAA-Gel establishes an immunosuppressive microenvironment, significantly prolonging graft survival. These findings demonstrate a potentially safer therapeutic strategy for maintaining sustained allograft function through localized immunomodulation.

Spinal cord interfaces hold promise in restoring motor function following spinal cord injury (SCI), yet current designs face trade-offs between the degree of invasiveness and interfacial impedance. Here, we present a magnetically actuated robotic spinal cord probe (RSCP) composed of a composite material combining MXene (Ti₃C₂T_x) with Poly(2,3-dihydrothieno-1,4-dioxin)-poly(styrenesulfonate) (PEDOT:PSS), referred to as MxP. This interface is integrated with a magnetic elastomer (ME) substrate to enable soft, remote, and minimally invasive actuation and positioning. We demonstrate that magnetic actuation achieves >5 mm deflection with modest fields (∼100 mT), sufficient to conform to spinal cord anatomy. Impedance measurements using a tissue-mimicking phantom reveal that magnetic positioning significantly reduces interfacial impedance by up to 27% within the biologically relevant frequency range (5–5000 Hz) for stimulation and recording. Furthermore, the MxP electrodes demonstrate superior electrochemical stability over 21 days in phosphate-buffered saline than its MXene counterpart. Stereotaxic implantation of the RSCP’s in mice followed by immunohistochemistry analysis revealed minimal gliosis and microglial activation over 3 weeks, confirming in vivo biocompatibility. This work presents magnetically actuated RSCP’s as a potential solution to the invasiveness-impedance trade-off in spinal cord interfaces, establishing a foundation for improved therapeutic outcomes in SCI treatment.

Mycobacterium tuberculosis (Mtb) remains a major global health threat, intensified by multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. We synthesized a series of N-benzoyl-arylthiourea derivatives (IITKDA1–20) as hybrids of isoniazid/pyrazinamide and ethionamide to explore their antimycobacterial potential. Our evaluation of synthesized library members for antimycobacterial activity has identified IITKDA10 (N-benzoyl-arylthiourea possessing p-(N-Boc)-thionamide) as the maximally effective inhibitor of Mtb (1 μg/mL MIC). Further, the physicochemical properties indicated a trend of high topological polar surface area (tPSA) and partition coefficient (ClogP) in the range of 3–4 was optimal for the compounds to be active against Mtb. Molecular docking of IITKDA10 into the InhA (enoyl-[acyl-carrier-protein] reductase) active site revealed strong binding (−9.63 kcal/mol), stabilized by hydrogen bonds and π-alkyl interactions. Further, crystal packing analysis indicated that hydrogen bonding networks guided supramolecular architecture, and structural planarity (e.g., IITKDA4, IITKDA8) correlated with higher activity. In contrast, twisted or L-shaped conformations (IITKDA2, IITKDA5) showed reduced potency. This study presents a structurally and functionally diverse set of N-benzoyl-arylthioureas with promising anti-TB activity, supported by structure–activity relationships, docking, and crystallographic insights.

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation and redox imbalance, has emerged as a promising strategy for treating drug-resistant cancers. However, its therapeutic efficacy is often limited by the antioxidant-rich tumor microenvironment (TME), which inhibits reactive oxygen species (ROS) accumulation. In this study, we introduced a tumor-responsive nanoplatform (MLCT) designed to synergistically amplify ferroptosis through a combination of iron catalysis, calcium overload, nitric oxide (NO) release, and photothermal stimulation. The MLCT platform consisted of mesoporous polydopamine (MPDA), calcium peroxide (CaO₂), l-arginine (LA), and a tannic acid-Fe³⁺ (TA-Fe) shell, facilitating TME-responsive release of therapeutic agents. In vitro, MLCT effectively depleted glutathione (GSH) and sustained NO generation, resulting in elevated ROS levels and mitochondrial dysfunction. Additionally, upon near-infrared (NIR) irradiation, localized hyperthermia further potentiated ferroptotic activity. In vivo, MLCT combined with NIR treatment resulted in an 86.34% reduction in tumor growth, with minimal systemic toxicity. These results highlighted the potential of MLCT as a precision-engineered ferroptosis platform for enhanced cancer therapy.

Carbon quantum dots, are characterized by their exceptional fluorescence properties, low toxicity, and broad potential in biological applications and bionanotechnology. In this study, carbon dots derived from Bletilla striata (BS-CDs) were synthesized to investigate their antioxidant activity, stability, and their effects on the growth of mung bean sprouts. The results showed that BS-CDs possess remarkable antioxidant properties and excellent stability. At lower concentrations, BS-CDs significantly promoted plant growth, whereas higher concentrations exerted inhibitory effects. The optimal concentration for growth enhancement was determined to be 0.4 mg/mL (an increase of 36.4% compared to the deionized water control group). These findings highlight the potential of BS-CDs as innovative agricultural supplements, leveraging their antioxidant activity and concentration-dependent effects to improve plant growth.

Acute open wounds are susceptible to hemorrhage and infection if not treated quickly and effectively. Unfortunately, most primary wound care treatment strategies lack the ability to deliver therapeutics into the wound volume with temporal and spatial stability. Existing technologies generally only perform one function (i.e., reduce bleeding), forcing first responders to rely on a series of time-consuming prehospital treatments in resource-limited situations. To overcome these challenges, we developed and evaluated a vancomycin- and tranexamic acid-loaded biopolymer-based medical foam (MF) composed of carboxymethyl cellulose (CMC). The medical foam’s physical characteristics, cytocompatibility, antifibrinolytic efficacy, and antimicrobial activity were evaluated to demonstrate in vitro feasibility and scientific validation data with experimentation. The MF exhibited rapid expansion (3.23× initial volume) and sustained structural stability (26.5 min) in vitro. When applied ex vivo, the foam significantly reduced bacterial load (>99%) and decreased blood loss by 87.5% compared to controls. These data support the foam’s potential to spatially and temporally fill irregular wound cavities, stabilize clot formation, and provide infection prophylaxis in austere or resource-limited environments. Results demonstrated that the MF is both safe to human tissues in vitro and effective at delivering hemostatic and antibiotic agents topically.