Journal of Materials Chemistry B最新文献

Triple-negative breast cancer (TNBC) remains a therapeutic challenge due to its aggressive nature, limited treatment options, and propensity for developing multidrug resistance (MDR). To overcome these limitations, a novel micelles-in-lipopolymersome nanocarrier system is developed herein for targeted drug delivery. Specifically, an epidermal growth factor receptor (EGFR)-targeted EGF peptide is conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG-NH₂) and subsequently incorporated into micelles, which significantly reduces the critical micelle concentration (CMC) and enhances the structural stability. The paclitaxel (PTX)-loaded micelles (designated Micelle@PTX) exhibit pronounced pH-sensitive behavior, being less stable under acidic conditions, thereby facilitating rapid drug release in a tumor-like microenvironment. To further improve its stability and control the drug release, Micelle@PTX is encapsulated within lipopolymersomes to obtain Lipo-Micelle@PTX particles with sizes ranging from 120 to 150 nm. Notably, the as-fabricated system effectively co-delivers hydrophobic PTX and hydrophilic irinotecan (CPT-11), thereby illustrating its versatility for combination chemotherapy. In vitro release experiments demonstrate that both PTX and CPT-11 are released more rapidly at pH 6.5 than at pH 7.4. Cellular uptake studies, supported by confocal microscopy and FACS analysis, reveal enhanced internalization of the EGFR-targeted nanocarriers in drug-resistant BT-20 LUC/MDR cells, thus resulting in improved cytotoxicity compared to free PTX. Preliminary in vivo studies further demonstrate that Lipo-Micelle@PTX significantly inhibits tumor growth compared to PTX alone, without inducing detectable systemic or organ toxicity. This study presents a promising platform for overcoming drug resistance in TNBC, with potential implications for targeted cancer therapy and improved clinical outcomes.

Antimicrobial peptides (AMPs) are a unique class of bioactive compounds with applications in antimicrobial therapy, anti-inflammatory regulation, and drug delivery. As antibiotic resistance escalates globally, AMPs have emerged as one of the most promising alternatives to conventional antibiotics. Nevertheless, their clinical utility is limited by pH-dependent instability and enzymatic degradation in vivo. Hydrogels, as versatile polymers, offer solutions through their tunable biological properties. Recent advances at the material-biomedical interface have spurred innovative strategies to engineer AMP hydrogels, overcoming intrinsic limitations. This review presents a comprehensive analysis and discussion of various synthetic approaches to antimicrobial peptide hydrogels, with particular emphasis on mechanisms involving the modulation of reactive oxygen species. Additionally, the current state of antimicrobial peptide hydrogels is explored within antifungal therapy, wound healing, cancer treatment, bioimaging, nucleic acid delivery, immunomodulation, and surgical implants. Finally, we offer a concise perspective on the future trajectory of antimicrobial peptide hydrogel research. We aim to provide a theoretical framework for ongoing studies in this domain and inspire innovative avenues for future investigations.

Hydrogels for bone regeneration have expanded the therapeutic approaches for bone injury repair by integrating traditional and novel biomaterials. However, this field urgently requires systematic research trend analysis. Based on multidimensional bibliometric mapping, this review conducted analyses including journal citations, international collaborations, spatiotemporal output distribution, and co-citation clustering. It revealed that the annual publication volume in the field of bone regeneration hydrogels has shown exponential growth, with increasing attention from the research community. Additionally, this study systematically reviewed hot biomaterials such as hydrogels loaded with mesenchymal stem cells (MSCs)/extracellular vesicles (EVs), hydrogels based on decellularized extracellular matrix (dECM), hydrogels based on silk fibroin (SF) and responsive hydrogels. It innovatively proposed five targeted strategies for bone repair material design-regulating bone homeostasis, modulating the bone immune microenvironment, promoting vascularized bone regeneration, regulating oxidative stress, and neural regulation. This strategic framework constructs a material-mechanism coupling model from the biological essence, providing a new research perspective for the field of bone regeneration hydrogels and laying the foundation for the development of future bone regeneration materials.

High-grade serous ovarian cancer (HGSOC) is a highly aggressive malignancy often diagnosed at an advanced stage due to the absence of early symptoms and effective diagnostic tools. Extracellular vesicles (EVs) secreted by tumour cells carry disease-specific biomarkers, offering potential for early detection. However, their low concentration in biological samples poses challenges for isolation and detection, necessitating highly sensitive and specific multiplexed assays for subsequent detection of multiple biomarkers. Herein, we report the design of metal–organic framework (MOF)-derived porous superparamagnetic iron oxide nanorods (MOF-IONRs) to construct a rapid and sensitive surface-enhanced Raman scattering (SERS)-based multiplexed assay to detect HGSOC-specific EV protein biomarkers in clinical samples. The high porosity and large surface area of MOF-IONRs enable enhanced antibody loading and efficient biomarker capture, while simultaneously enriching SERS nanotags for signal amplification. Their intrinsic magnetic properties facilitate straightforward magnet-based isolation and purification of EVs. Additionally, the incorporation of mesoporous gold nanoparticle (mAuNP)-based SERS nanotags further enhance the Raman signal intensity. This integrated platform exhibits a limit of detection (LoD) of 2.13 EVs per µL with excellent reproducibility (%RSD < 10%, n = 3). Clinical validation successfully distinguishes ovarian cancer patients from healthy controls, highlighting its diagnostic accuracy and reliability. This multiplexed platform shows promise as a liquid biopsy for the early diagnosis of HGSOC, enabling rapid, cost-effective, and highly sensitive detection of EV-associated biomarkers in complex clinical samples. Moreover, integration with a handheld Raman spectrometer provides portability and compatibility with point-of-care (POC) testing, highlighting its promise as a transformative tool in ovarian cancer diagnostics and patient management.

Chemodynamic therapy (CDT) and enzyme dynamic therapy (EDT) are effective treatment methods that kill tumor cells by producing large amounts of reactive oxygen species (ROS). However, the endogenous hydrogen peroxide (H₂O₂) concentration in tumors is insufficient, limiting the production of ROS and weakening the therapeutic effects of CDT and EDT. Therefore, a nanoplatform (CeO₂@CPT@CPO) based on mesoporous cerium dioxide (CeO₂) was designed to deliver camptothecin (CPT) and chloroperoxidase (CPO), thereby achieving synergistic CDT, EDT, and pharmacological chemotherapy of ovarian cancer. CeO₂@CPT@CPO possesses peroxidase (POD) and CPO-like activities, which can catalyze H₂O₂ to produce a large amount of ROS to kill tumor cells. CPT, as a chemotherapeutic drug, can activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate H₂O₂, thereby enhancing the therapeutic efficacy of CDT and EDT. Meanwhile, CeO₂@CPT@CPO with catalase (CAT)-like activity can catalyze H₂O₂ to produce oxygen (O₂) to alleviate hypoxia in the tumor microenvironment (TME). Additionally, CeO₂@CPT@CPO is capable of depleting intracellular glutathione (GSH), thereby safeguarding the stable presence of ROS and contributing to their further accumulation. Finally, the synergistic effect of CDT, EDT, and chemotherapy leads to mitochondrial and DNA damage, which in turn promotes apoptosis of tumor cells. The potent tumor-suppressive effect of CeO₂@CPT@CPO highlights its potential for synergistic ovarian cancer therapy.

Ocular drug delivery is challenging due to physical and physiological barriers, such as the corneal epithelium and blood–retinal barrier, resulting in limited bioavailability (<5% for eye drops) and fast degradation. For the reason of improving drug delivery to the anterior and posterior ocular segments, this review attempts to assess hydrogel-based systems as versatile systems to overcome these barriers. We thoroughly explore physicochemical and performance characterization approaches (e.g., swelling, rheology, drug release kinetics), hydrogel fabrication methods (e.g., chemical crosslinking, 3D printing), and their uses in new and commercial products. Significant advances highlight the controlled release, mucoadhesion, and biocompatibility of hydrogels, which allow prolonged drug delivery as demonstrated by commercial products such as DEXTENZA® and ReSure® Sealant for corneal sealing and post-operative inflammation control. New technologies provide greater accuracy and less invasiveness. Examples include bioengineered hydrogels for retinal regeneration, systems integrated with nanotechnology, and stimuli-responsive hydrogels (such as pH-sensitive chitosan for glaucoma). By addressing mechanical stability and regulatory criteria, characterization techniques guarantee the suitability of the hydrogel for ocular applications. Hydrogels exhibit considerable promise for personal and least invasive treatments, despite challenges like scalability and high production costs. With implications for improving clinical outcomes and patient compliance through novel biomaterials, this review highlights the important role of hydrogels in ocular drug delivery and offers an outline for future advancements in the treatment of diseases like glaucoma, age-related macular degeneration, and dry eye syndrome.

Eyedrop-based delivery of therapeutic agents provides promising benefits in treating ocular diseases. Conventional topical delivery strategies rely on the passive diffusion of drugs, which is limited in the retention of the drug on the cornea of the eye. The application of nanoparticles promises ocular delivery but is constrained by the physiological barriers of the ocular surface. Here, we demonstrate the application of an eyedrop containing nanorobots for the active retention of drugs for ocular therapy. The nanorobots were fabricated by encapsulating AmB in poly(lactic-co-glycolic acid) PLGA nanoparticles, followed by urease surface functionalization. The individual and swarm movement of the nanorobots is driven by enzymatic reactions through the catalytic decomposition of urease in tears. This active mobility prolonged drug retention by 4-fold compared with passive nanoparticles and promoted corneal healing in fungal keratitis models. Thus, the AmB-loaded nanorobots effectively prolong corneal retention and enhance the therapeutic effect against fungal keratitis.

Hemodialysis is indispensable for patients with end-stage renal disease (ESRD). Yet, the performance of conventional polymeric membranes is restricted by protein adsorption, poor hemocompatibility, and thrombo-inflammatory responses. We hypothesized that functional modification of a cellulose acetate (CA) matrix with selected additives could overcome these limitations. By enhancing hydrophilicity, permeability, and anticoagulant behavior, such membranes could provide improved therapeutic potential. To evaluate this, CA-based flat sheet membranes (FSMs) were fabricated through non-solvent-induced phase separation and scaled into hollow fiber membranes (HFMs) by dry-wet jet spinning. Polyethyleneimine (PEI) and polyethylene glycol (PEG) were incorporated to adjust the pore structure, surface chemistry, and transport properties. Citric acid and gelatin were introduced as anticoagulant agents to assess their impact on blood compatibility. A comprehensive characterization was carried out, including SEM, FESEM, AFM, FTIR, tensile testing, porosity measurements, and contact angle analysis. Membrane performance was evaluated through pure water flux and dialysis simulations with urea, creatinine, lysozyme, and bovine serum albumin (BSA). Among the FSMs, CA-4 achieved a water flux of 54.40 L m⁻² h⁻¹ at 2 bar, with 78% urea clearance, 31% creatinine clearance, and 94% BSA retention. Transition to a hollow fiber geometry enhanced scalability and clinical relevance. HF-2 displayed a flux of 83.34 L m⁻² h⁻¹ at 2 bar, ∼66.5% urea clearance, and 90.3% protein retention. These values indicate a clinically significant balance between permeability and selectivity. Biocompatibility testing showed that citric acid-modified membranes reduced platelet adhesion and thrombus formation, while maintaining hemolysis ratios below the ASTM F-756-08 threshold of 5.5%. Gelatin-modified membranes lowered hemolysis up to 2.4% but promoted protein adsorption and platelet adhesion. This makes them more suited for regenerative applications than for dialysis. Overall, the results validate the hypothesis that the integration of PEI, PEG, citric acid, and gelatin into CA membranes enhances both physicochemical and biological performance. The scalable fabrication approach presented here provides a framework for next-generation hemodialysis membranes. These membranes improve solute clearance, minimize blood incompatibility, and support safer renal replacement therapy.

Cerebral palsy (CP), the leading cause of lifelong motor disability in children, lacks effective neural regeneration therapies. Current treatments only alleviate symptoms, and while neural stem cell (NSC) transplantation shows promise, its efficacy is hindered by poor post-transplant cell survival and differentiation. To overcome this, we developed an injectable, conductive hydrogel (MS-gel) mimicking the brain's electroactive extracellular matrix. The MS-gel integrates oxidized alginate and silk fibroin (MOA/TOA/SF) through dual-crosslinking (Schiff-base and photopolymerization), enabling rapid in situ gelation (<60 s) and stable conductivity (1.19 ± 0.02 mS cm⁻¹) matching neural tissue properties. In vitro, the MS-gel maintained >90% NSC viability and enhanced neuronal differentiation (1.67-fold increase in β-III tubulin). In CP rat models, NSC-loaded MS-gel implantation improved motor function (88% longer rotarod latency) and cognition (80% shorter Morris water maze escape time). Proteomics revealed that NSCs@MS-gel promotes neural circuit repair via enhanced cellular clearance, ion homeostasis, cytoskeletal reorganization, synaptic restoration, and myelin integrity. This study presents the first integrated platform combining light-controlled gelation, tissue-matched electroactivity, and cytoprotection, offering significant potential for CP and other neurological disorder therapies.

Neuronal cells are in most parts exempt from the daily flux of cell birth and death. The identification of dead neuronal cells is essential for facilitating our understanding of the types, mechanisms, and roles of neuronal cell death in physiology and pathology and for the investigation and treatment of neurodegenerative diseases. It is highly desirable to fabricate fluorescent probes with strong binding affinity, high brightness, and long-wavelength excitation to identify dead neuronal cells. In this study, we developed a water-soluble, polycationic two-photon fluorescent probe (BTD-V) for identifying dead neuronal cells. The hydrophilic nature and positive-charged polycation enabled BTD-V to selectively accumulate in the nuclei of dead cells. BTD-V also exhibited a large Stokes shift of 180 nm, enhanced high brightness of 13 251 M⁻¹ cm⁻¹ upon binding with DNA, and strong DNA-binding ability with an apparent dissociation constant of 0.75 nM. Based on these properties, this probe could be used to effectively monitor different types of neuronal cell death induced by hydrogen peroxide and glutamate due to differences in the nuclear morphologies. The BTD-V probe could also be used for two-photon brain imaging, enabling the monitoring of traumatic brain injury (TBI) in mice by staining the dead nuclei of paraffin sections and cryosections. This research provides a promising DNA probe for identifying the dead cells, discriminating the cell death type, and monitoring the neuronal-related diseases.