Journal of materials chemistry. B最新文献

Spinal cord injury (SCI) encompasses a series of pathophysiological processes, including inflammation, apoptosis, autophagy, and pyroptosis, leading to an imbalance in the microenvironment. The microenvironment following injury inhibits axonal regeneration, ultimately resulting in the loss of neurological function. Among these pathological processes, inflammation plays a critical role in the recovery from SCI. The inflammatory cascade triggered by SCI leads to cell apoptosis, cell death, and impaired angiogenesis, which collectively hinder axonal regeneration. In recent years, nano-enzymes exhibiting Prussian blue enzyme-like peroxidase activity have garnered significant attention as alternatives to natural enzymes in therapeutic applications, biosensing, and environmental remediation. Schisandra, a traditional Chinese medicine, contains schisantherin B as its principal component, which has been reported to possess neuroprotective effects in various neurological diseases. In this study, we designed a Prussian blue nanozyme drug delivery system, a schisantherin B-loaded Prussian blue nanozyme (SchB@PBzyme), for the treatment of SCI. Our findings indicate that the SchB@PBzyme significantly suppresses the inflammatory response and promotes neural remodeling, thereby offering a novel treatment strategy for SCI.

The alarming rise in antibiotic resistance necessitates the urgent development of novel therapeutic agents. Herein, we report a bifunctional approach to synthesize two series of dihydrofurocoumarins (DHFCs), one incorporating naphthalimide and the other featuring coumarin analogues, designed to explore their antibacterial potential and ability to combat antibiotic resistance through structural diversification. Preliminary assessments reveal that some synthesized analogues exhibit significant antibacterial potency. Notably, analogues with electron-withdrawing substituents, particularly 16b and 21e (MIC = 1.56 µg mL^-1), display outstanding activity against E. coli, demonstrating a higher potency than the marketed antibiotic amoxicillin. The low-frequency resistance observed for analogues 16b and 21e, as evidenced by stable MIC values even after extended passages, may be attributed to their rapid bactericidal action. Additionally, both analogues strongly inhibit biofilm formation, disrupting a critical pathway involved in the development of drug resistance. Mechanistic investigations revealed that both analogues effectively disrupt bacterial membranes, triggering cytoplasmic leakage and a significant loss of metabolic activity. They also induce reactive oxygen species (ROS) generation, catalyzing the oxidation of GSH to GSSG, thereby diminishing cellular GSH activity and weakening the bacterial antioxidant defense system, ultimately leading to oxidative damage and cell death. Active analogues were evaluated for their binding affinity to human serum albumin (HSA), demonstrating a balanced binding profile with optimal binding constants, indicative of their potential to facilitate targeted delivery without compromising drug release at the intended site. Site marker drug displacement studies further identified their binding sites, showing that 16b exhibited a preference for Sudlow site I, while 21e selectively associated with the heme site on HSA. Molecular docking studies further corroborated these findings, revealing perfect alignment with experimental results. Further investigations indicated that both active analogues intercalated into DNA, forming DNA-16b/21e complexes that disrupted essential biological functions, leading to bacterial death. Quantum chemical insights revealed a narrower HOMO-LUMO energy gap, facilitating electronic transitions and enhancing molecular reactivity, which may be pivotal for their antibacterial effectiveness. Amidst the limitations of conventional antibiotics, these findings underscore the potential of dihydrofurocoumarins as potent multitarget, broad-spectrum antibacterial agents. Their ability to impair bacterial defense mechanisms and combat persistent pathogens presents a promising avenue for advancing antibacterial therapeutics, paving the way for further clinical exploration and the development of novel antibacterial analogues.

Modulating membrane permeability and morphology remains a central challenge in the design of responsive colloidal and self-assembled systems. Here, we present a strategy that integrates fluorescently labelled, photoswitchable amphiphiles into lipid vesicles to enable real-time visualization of dynamic membrane behavior and light-triggered cargo release. A novel amphiphilic molecule based on an azobenzene core was synthesized and functionalized with the fluorophore Nile red. This compound was incorporated into giant and large unilamellar vesicles (GUVs and LUVs) composed primarily of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) lipids. The response of the vesicles to alternating UV and visible light was characterized using confocal microscopy, fluorescence spectroscopy, and molecular dynamics simulations. Upon irradiation, vesicles exhibited reversible morphological transformations including budding, swelling, and prolate deformation. Fluorescence imaging confirmed efficient incorporation of the amphiphiles into lipid membranes, and the solvatochromic behavior of Nile red enabled distinction between lipid domains. Simulations revealed that Z-isomerization induces asymmetric expansion of the outer membrane leaflet, increasing surface tension and bending modulus, key drivers of the observed shape changes. Furthermore, cargo release assays with LUVs demonstrated controlled, reversible light-induced permeability. The temporal mismatch between morphological response and ROS (reactive oxygen species) generation, along with the reversibility of the effects, supports a non-oxidative, photomechanical mechanism. Based on these findings, fluorescent photoswitchable amphiphiles can be considered as powerful tools for both functional membrane engineering and the study of the relationship between molecular-level interactions, polarity, and macroscale membrane behavior.

Hexagonal boron nitride nanosheets (BNNSs), produced via a simple NaOH-assisted liquid exfoliation of bulk BN (h-BN), have been employed for the first time for the electrochemical (EC) detection of sulfamethoxazole (SMZ), a widely detected antibiotic in surface and groundwater. The resulting BNNS-modified glassy carbon electrode (BNNS/GCE) exhibited enhanced sensitivity compared to the bare GCE, BNNS_(H2O)/GCE, and h-BN/GCE, and a detection limit of 1 nM. The enhanced performance of the BNNS/GCE is attributed to its nanosheet morphology, the NaOH-introduced functional groups, which promoted hydrogen bonding, and Lewis acid-base interactions between the intermediate acid boron (B) with the intermediate basic N-functional groups in SMZ, thus imparting strong affinity and efficient charge transfer with SMZ. The sensor demonstrated selectivity towards SMZ in the presence of potential interferents such as antibiotics, metal ions, and biological molecules. The BNNS/GCE showed repeatability and stability, and exhibited performance in real water samples with reliable recovery rates. This work highlights a cost-effective, environmentally friendly, and scalable EC sensor material for trace-level antibiotic monitoring in complex environmental matrices.

Melanoma is a highly aggressive skin cancer that often develops resistance to chemotherapy, underscoring the need for new treatment strategies. Here we evaluate plasmonic gold nanocapsules (AuNCs) as photoresponsive agents for two-photon luminescence-assisted photothermal therapy in chemoresistant melanoma models. The performance of the AuNCs was assessed in two-dimensional cell cultures, three-dimensional paclitaxel-resistant B16-F10 melanoma spheroids, and a subcutaneous melanoma mouse model under near-infrared excitation. In vitro, AuNCs alone exhibited no cytotoxicity, but under 830 nm two-photon excitation, they produced strong two-photon luminescence and thermal effects that increased with nanocapsule concentration and laser power. This led to transient oxidative stress, apoptosis induction, and effective melanoma cell ablation under optimal conditions (80 μg mL^-1 AuNCs, 12 mW laser power). In vivo, the route of nanoparticle administration proved decisive. A single 4-min 806 nm irradiation after intratumoral injection uniformly heated the lesion (≈45-50 °C), yielded durable tumour eradication, and sequestered >99% of detected gold in the necrotic scab, with only trace renal clearance. In contrast, the same laser fluence after peritumoral injection generated a superficial hot rim, spared the tumour core, allowing eventual regrowth, and left ∼65% of the injected gold systemically redistributed, mainly in the spleen and liver. These findings highlight the potential of AuNCs as potent, image-guided photothermal agents for chemoresistant melanoma, offering targeted tumor destruction with limited systemic exposure. They reveal the injection route is a critical determinant of both therapeutic success and nanoparticle biodistribution.

The development of stimuli-responsive amphiphilic block copolymers and their nanoassemblies/nanogels integrated with degradable covalent chemistry undergoing chemical transitions has been extensively explored as a promising platform for tumor-targeting controlled/enhanced drug delivery. The conjugate aromatic imine bond is unique in responding to acidic pH through acid-catalyzed hydrolysis and visible light through photo-induced E/Z isomerization, thus allowing for a dual acid-light response via a single conjugate aromatic imine bond. Herein, we report a robust strategy for fabricating well-defined core-crosslinked nanogels bearing extended conjugate aromatic imine linkages that exhibit controlled degradation in response to acidic pH and visible light. This approach utilizes the pre-crosslinking of a poly(ethylene glycol)-based block copolymer bearing reactive imidazole pendants with a diol crosslinker bearing an extended conjugate aromatic imine, followed by the mechanical dispersion of the formed crosslinked polymers in an aqueous solution. The fabricated core-crosslinked nanogels with a hydrodynamic diameter of 119 nm are non-cytotoxic, colloidally stable, and capable of encapsulating cancer drug curcumin. They exhibit controlled/enhanced release of encapsulated curcumin at pH = 5 (acidic) or upon irradiation with visible light (λ = 420 nm) as well as exhibit promisingly accelerated and synergistic release under the combination of the above conditions. Furthermore, curcumin-loaded nanogels reduce cell viability in a controlled manner, unlike free drugs. This simplified yet efficient synthetic approach paves the way for the development of smart nanocarriers with potential applications in controlled drug release and cancer therapy.

Self-powered piezoelectric materials can generate continuous electrical stimulation in response to weak mechanical forces, holding great potential for accelerating wound healing. Herein, a multifunctional ZIF-8/PVDF piezoelectric fiber dressing was fabricated using the electrospinning method for generating electrical stimulation to enhance the endogenous electric field at the wound site. The incorporation of ZIF-8 nanoparticles and the stretching polarization effect of electrospinning on the fibers promote the formation of the piezoelectric β-phase in PVDF, leading to enhanced piezoelectricity. The improved piezoelectric and conductive properties collectively enhance the output electrical signals of the fiber. The short-circuit voltage and open-circuit current of the 5% ZIF-8/PVDF fiber were 2.97 V and 13.7 nA, respectively, showing significant improvement compared to the pure PVDF fiber. In vitro experiments demonstrate that the fiber can generate reactive oxygen species (ROS) and release Zn²⁺ under ultrasonic conditions, which together with electrical stimulation endows the dressing with effective antibacterial, anti-inflammatory, and angiogenic effects. In vivo studies of infected skin defect models demonstrated that the ZIF-8/PVDF fiber dressing can significantly inhibit bacterial infection, regulate inflammatory responses, enhance angiogenesis, and ultimately accelerate the infected wound healing process. This developed multifunctional piezoelectric fiber dressing provides an effective strategy for infected wound repair.

Polymer nanotherapeutics have gained prominent attention in drug delivery systems. Polymers are widely explored tools to improve the solubility, stability, bioavailability, and prolonged circulation of therapeutic agents. Abraxane, Myocet, DaunoXome, and Doxil are some examples of successful polymeric nanocarriers approved for cancer treatment. Medicinal chemists have access to a vast array of nanomaterials that include polymeric nanoparticles (PNPs), polymeric micelles (PMCs), prodrugs, liposomes, and dendrimers. Polyethylene glycol (PEG), pHPMA (poly-N-2 hydroxypropyl methacrylamide), polyethylene, polystyrene, and other compounds have been extensively used for drug delivery. This review highlights the importance of pHPMA in nanodrug delivery. First, we review the chemical properties, pharmacology, and pharmacokinetics of pHPMA, followed by its synthetic routes of preparation. Second, we discuss pHPMA-based nanocarriers and their therapeutic efficacy in cancer. In addition, we present the clinical status and future prospects of pHPMA in combination with immunotherapy. We aim to provide comprehensive insights into the current pHPMA nanotherapeutics to facilitate future development.

Bacterial biofilms remain a major challenge in treating persistent infections due to their dense extracellular matrix and inherent antibiotic resistance. Herein, we propose a light-responsive nanoparticle system (PNO@Ir) that integrates a nitric oxide (NO) donor polymer (PNO) with the photosensitizer fac-Ir(ppy)₃. Upon green light irradiation, NO release and activation of primary amine-containing antibacterial polymers are triggered via a dual mechanism involving triplet-triplet energy transfer (TTET) and photoinduced electron transfer (PeT). Under mildly acidic and hypoxic conditions, protonation of the exposed amines induces nanoparticle reorganization, leading to surface charge reversal and enhanced bacterial affinity. Both in vitro and in vivo studies, including a murine wound infection model, demonstrate that this cascade-activation strategy disrupts methicillin-resistant Staphylococcus aureus (MRSA) biofilms. This work presents a synergistic and spatiotemporally controllable platform for NO delivery and antibacterial polymer activation, offering significant potential for combating antibiotic-resistant bacterial infections.

Hollow fiber membranes (HFMs) are critical components in hemodialysis and bioartificial kidney (BAK) applications, with ongoing research focused on optimizing biomaterials for improved performance. In this study, polyethersulfone (PES) HFMs were modified by incorporating titanium dioxide (TiO₂) and graphene oxide (GO) during the spinning process. This approach leverages the non-toxicity, hydrophilicity, and dispersion stability of TiO₂ alongside the large surface area of GO to enhance membrane properties. Characterization and performance evaluations demonstrated that TiO₂/GO-doped PES HFMs exhibit superior biocompatibility and hemocompatibility compared to plain PES, TiO₂/PES, and GO/PES membranes. Confocal microscopy revealed improved HEK293 cell attachment and proliferation, corroborated by MTT assays showing higher cell viability and flow cytometry indicating no cytotoxic effects. Hemocompatibility tests confirmed negligible hemolysis and anti-inflammatory properties, making the membranes suitable for blood-contacting applications. Furthermore, separation performance analyses highlighted TG(0.5/1.5) as the optimal composition, offering a balance of enhanced toxin removal and cell compatibility. These findings establish TiO₂/GO-doped PES HFMs as promising candidates for BAK and hemodialysis, combining excellent biocompatibility, hemocompatibility, and separation efficiency.