Journal of materials chemistry. B最新文献

This study introduces two new ratiometric probes, AH+ and BH+, designed to monitor mitochondrial pH dynamics. Derived from IR-780 iodide, these probes incorporate imidazole, hydroxy-xanthene, and hemicyanine groups. Owing to their positively charged hemicyanine groups, both probes selectively accumulate in mitochondria through electrostatic interactions. Their sensing mechanism is governed by deprotonation-induced π-conjugation rearrangements, enabling dual-emission fluorescence for real-time visualization of mitochondrial pH fluctuations. Monitoring of various cellular processes, including mitophagy, hypoxia, oxidative stress, and mitochondrial dysfunction induced by metformin, is reported. In their protonated states (AH+ and BH+), the probes exhibit large Stokes shifts (>90 nm) due to excited state intramolecular proton transfer (ESIPT). In contrast, the unprotonated forms (A and B) show anti-Stokes shifts. While theoretical calculations using the APFD/6-311+g(d,p) functional/basis set were conducted to simulate these effects, the results were inconsistent with experimental findings. The probes' suitability for measuring mitochondrial pH in HeLa cells was confirmed through a series of tests for photostability, selectivity, reversibility, and cytotoxicity. Colocalization experiments yielded high Pearson Correlation Coefficients (PCC) of 0.96 for AH+ and 0.93 for BH+, affirming their specific mitochondrial targeting. The probes successfully measured pH changes in HeLa cells under various conditions, including changes in buffer pH, starvation, oxygen deprivation, and chemical treatments with NAC, FCCP, and H₂O₂. Their ability to sense pH was also validated in vivo using Drosophila melanogaster larvae. Significantly, treatment with metformin was shown to alter mitochondrial pH levels, demonstrating the probes' utility in studying drug effects. Collectively, these findings establish AH+ and BH+ as powerful tools for probing mitochondrial function and cellular stress responses, offering new opportunities to explore fundamental mechanisms underlying health and disease.

Conductive hydrogels are promising candidates for neural bioelectrodes due to their softness, ionic permeability, and reduced mechanical mismatch with neural tissue. However, pristine biopolymer matrices such as alginate-gelatin (Alg-GEL) lack sufficient electrical functionality. Here, Alg-GEL hydrogels incorporating PEDOT:PSS, polypyrrole (PPy/PSS), or both were developed via blending and in situ polymerization, yielding a tunable family of soft, electroactive materials. The hydrogels exhibited Young's moduli of 5-70 kPa, depending on polymer loading, while electrical conductivities ranged from 0.1 to 3.7 S cm^-1, with the highest values observed in PEDOT-PPy hybrids. Electrochemical measurements showed impedance values of 380-830 Ω cm² at 1 kHz, an electrochemical stability window of approximately -0.85 to +1.2 V vs. Ag/AgCl_sat, and current injection limits reaching 4 mA, comparable to platinum electrodes. Swelling studies indicated that PEDOT-modified hydrogels achieved 41-56% swelling after 24 hours. PPy-based hydrogels swelled to approximately 97% and hybrid systems showed behavior dependent on their composition. All conductive formulations demonstrated improved long-term stability compared to pristine Alg-GEL, which gradually lost mass over 28 days of incubation. In contrast, hydrogels containing PEDOT and PPy maintained nearly constant wet weight, consistent with the formation of interpenetrating networks that prevented polymer degradation and leaching. Biological evaluation with NIH3T3 fibroblasts showed that all hydrogels were cytocompatible. PPy-only and PPy-PEDOT hybrids supported higher metabolic activity and more attached and spread cells after 7 days compared to Alg-GEL, while PEDOT-only samples showed similar or slightly reduced cell activity. These results confirm excellent cytocompatibility and suggest that PPy-rich domains improve cell-material interactions. Overall, PEDOT- and PPy-modified Alg-GEL hydrogels offer high conductivity, softness, electrochemical stability, long-term durability, and biocompatibility, creating a versatile and adjustable platform for next-generation soft neural interfaces.

To address the rapid systemic clearance and limited targeting efficiency of particulate drug delivery systems, localized drug delivery systems combining injectable hydrogels and nanoparticles have emerged as a promising alternative. This study introduces a photo-responsive multi-scale composite hydrogel platform for localized delivery of chemotherapeutic agents. In this study, doxorubicin-loaded photothermal nanoparticles (DOX@polydopamine@P(NIPAAm-co-AM), abbreviated as DPN) are prepared via a free radical polymerization route. Subsequently, they are incorporated into a thermosensitive PLGA-PEG-PLGA matrix to obtain the composite hydrogel (termed DPNP). The injectable DPNP hydrogel rapidly undergoes gelation as the temperature rises to the physiological level and forms an in situ depot at the targeted tissue due to the thermoresponsive sol-gel transition of the PLGA-PEG-PLGA matrix. Upon exposure to near-infrared light, polydopamine generates heat that induces a volume-phase transition of the DPN nanogels, thereby producing a precisely light-triggered release profile. The drug release rate can reach 87%. In the absence of light, the system maintains a sustained basal release rate. Overall, we have successfully developed a localized and spatiotemporally regulated drug delivery system capable of rapid NIR-triggered release coupled with sustained long-term release. The tumor suppression rate was 98.77%, providing a promising platform for precision-controlled cancer therapy.

Gastric mucosal injury is aggravated by sustained acid secretion, while conventional oral therapeutics suffer from limited bioavailability and lack intrinsic barrier properties. To overcome these challenges, we synthesized an injectable, acid-stable and antioxidant hydrogel (HDSCP) for ulcer repair. The system integrated a dynamic Schiff base network formed by dopamine-modified oxidized hyaluronic acid (HD) and carboxymethyl chitosan (CMCS) with polydopamine nanoparticles encapsulating ranitidine hydrochloride (PDR). Sodium alginate (SA) was incorporated to enhance acid resistance via electrostatic force. The dopamine group endowed the hydrogel with superior adhesion and antioxidant activity. Our HDSCP hydrogel promotes mucosal regeneration through two synergistic mechanisms: scavenging reactive oxygen species (ROS) to alleviate inflammation and establishing a protective barrier against gastric acid. The Transwell gastric acid barrier experiment demonstrated that the HDSCP hydrogel could mitigate the impact of gastric acid on cell viability and proliferation, thereby enhancing the cell survival rate. In vivo evaluation in an ethanol-induced rat gastric injury model confirmed that HDSCP significantly accelerated mucosal repair and regeneration. Overall, the HDSCP hydrogel offers a strategy for improving gastric mucosal integrity through its physical barrier function and ROS scavenging ability.

Atherosclerosis currently lacks effective therapeutic strategies specifically targeting and inhibiting foam cell formation. In this study, we engineered a macrophage nanoparticle composite drug delivery system that utilizes macrophages for competitive lipid uptake, coupled with ROS-responsive statin nanoparticles aimed at inhibiting cholesterol synthesis. This integrated system embodies a "smart immunomodulatory" approach, leveraging the inherent activity and targeted capabilities of immune cells. Experimental results demonstrated that this system significantly reduced lipid accumulation within foam cells by inhibiting cholesterol uptake, promoting cholesterol efflux and inhibition of apoptosis. These effects were mediated through microenvironmental optimization and upregulation of ABCA-1 and SR-BI expression. In an APOE knockout mouse model of atherosclerosis, the system effectively lowered lipid levels, modulated inflammatory responses, and significantly reduced foam cell formation and atherosclerotic plaque development. The system enhanced Treg cell proliferation and TGF-β secretion. Moreover, the system demonstrated high biocompatibility and therapeutic efficacy, training macrophages to revert to a low-lipid and M2 phenotype. This targeted drug delivery system integrates multiple therapeutic mechanisms, including inhibition of cholesterol uptake, enhancement of cholesterol efflux, and immunomodulation, providing a promising new strategy for the treatment of atherosclerosis.

The therapeutic performance of drugs is often limited by the inefficient targeting/delivery to intracellular targets. This study presents the engineered polymeric nanomicelle-based nuclear delivery of molecular sonosensitizers with enhanced therapeutic performance under ultrasound exposure. A nanocarrier was designed with exposed guanidinium groups that interact with cell membrane phosphates, enabling direct translocation into the cytosol and delivering the molecular sonosensitizer to the nucleus, bypassing endocytosis and lysosomal trapping. The nuclear delivery of sonosensitizers offers apoptotic cell death upon ultrasound exposure by producing reactive oxygen species around the nucleus. Control nanocarrier-based cytosolic delivery of the sonosensitizer showed 4 times lower cytotoxicity under similar conditions. Our findings demonstrate the potential of subcellular targeting/delivery for enhanced therapeutic performance.

Zwitterionic polymer coatings have been widely explored for the construction of bio-inactive surfaces. However, many conventional zwitterionic polymers exhibit reduced functionality under long-term use owing to the hydrolysis of ester linkages. Sulfobetaine-type polymers also display enhanced interchain interactions with increasing molecular weight, which can induce water insolubility and aggregation. In this study, we synthesized a new zwitterionic monomer, sulfoisobutylbetaine acrylamide (SBBAm), based on a molecular design that (i) connects the vinyl group and the zwitterionic side chain through a hydrolysis-stable amide linkage and (ii) introduces a branched isobutyl linker between the anionic and cationic moieties to suppress interchain association. Copolymers of SBBAm with a silane-coupling monomer were prepared and immobilized on glass substrates to fabricate zwitterionic coatings. Bio-inactivity was evaluated by protein adsorption and cell adhesion assays, and durability was examined by long-term incubation in phosphate-buffered saline (PBS) at 37 °C. SBBAm-based coatings maintained low protein adsorption and cell adhesion even after 1 year in PBS, whereas coatings from conventional zwitterionic monomers showed a decrease in bio-inactivity after 1 week. A comparison with a sulfopropylbetaine-type polymer confirmed the effectiveness of the isobutyl linker. These results provide molecular design guidelines for sulfobetaine-based zwitterionic materials with long-term durable bio-inactive surfaces.

Colorectal cancer (CRC) chemotherapy faces challenges such as poor gastrointestinal stability, low targeting efficiency, severe toxicity, and complex protocols. Recent pH-responsive nanocarriers mainly improve environmental stability but lack intelligent control. This study introduces a novel two-step "one-pot" aqueous synthesis strategy to create dual-targeting core-shell nanoparticles (LTDR-DS NPs) that are both efficient and environmentally friendly. The core contains a lysine-tannic acid conjugate and D-galactose, while the shell is a pH-responsive dopamine-alginate sodium (DA-SA) "smart armor". This design enables spatiotemporal targeting, combining pH responsiveness, precise delivery, and multi-mechanistic synergy. Unlike traditional nanocarriers, LTDR-DS NPs co-optimize stability and targeting, overcoming the dual challenges of poor stability and low targeting efficiency. They offer a groundbreaking, low-toxicity treatment strategy with high potential for clinical translation, enhancing therapeutic efficacy while reducing systemic toxicity and advancing CRC chemotherapy.

One of the challenges in antibiotic therapy is the development of bacterial resistance. It is urgent to develop new alternative antibacterial treatment strategies. Recently, researchers have paid close attention to carbon monoxide (CO) therapy, which can kill bacteria even in biofilms effectively, without drug resistance. The key to CO antibacterial activity lies in identifying carbon monoxide releasing molecules (CORMs) to achieve targeted delivery and controlled release. In this review, we elucidate the antibacterial mechanisms and design principles of CORMs. Furthermore, methods for controlled release and detection of CO are also summarized. CORMs enter bacterial cells, release CO inside the cells to inhibit bacterial respiration, and simultaneously interfere with bacterial metabolism and overall physiological functions. The integration of CO or CORMs with macromolecules or nanomaterials has improved the stability and release duration of CO delivery, to some extent achieving targeted delivery and enhancing biological safety. This review will provide guidance for the design and synthesis of new CORMs, which will promote the clinical therapy of CO.

Acne is a common chronic inflammatory skin disease associated with Cutibacterium acnes (C. acnes). Although photodynamic therapy (PDT) effectively improves acne, the transdermal delivery of photosensitizers and limited light penetration through the skin restrict its therapeutic efficacy. In this study, we developed a dual-functional flexible microneedle patch using 3D printing technology, capable of simultaneously delivering the photosensitizer 5-aminolevulinic acid (ALA) and blue light. The microneedle patch exhibits favorable mechanical properties (a fracture force of 2.47 N per patch and a drug loading capacity of 655 ± 0 µg per patch) and increases the light penetration depth in tissue by 128.6%. The combination of the microneedle patch and blue light achieved an antibacterial rate of 97.10 ± 1.1% against C. acnes in vitro. In animal experiments, this strategy resulted in significantly smaller acne lesions by day 7 (size: 1.53 ± 0.30 mm; thickness score: 0.20 ± 0.45; n = 5 per group, P < 0.05), with no significant adverse effects observed during the experimental period. Our preclinical findings demonstrate that this dual-function microneedle patch provides proof-of-concept for its future development as a novel integrated platform for PDT.