Journal of Materials Chemistry B最新文献

Immunoassays of antibodies are crucial for infection and disease diagnosis, therapeutic drug monitoring, and other purposes. For enhancing immunoassay reliability, the development of efficient solid supports is important. In this study, we propose water-dispersible, antibiofouling, and post-functionalizable cello-oligosaccharide nanosheets as a solid support for enzyme-linked immunosorbent assay (ELISA) immunoassays of anti-poly(ethylene glycol) (PEG) antibodies. A series of nanosheets exposing oligo(ethylene glycol) (OEG) chains of varying chain lengths and conjugation rates were synthesized in two steps: an enzyme-catalyzed oligomerization reaction for the synthesis of propargylated cello-oligosaccharide nanosheets and a subsequent click reaction for the conjugation of OEGs. The antibiofouling properties of the propargylated cello-oligosaccharide nanosheets allowed detergent-free ELISAs of two monoclonal anti-PEG antibodies, providing results consistent with their reported binding specificities. Moreover, remarkable results were obtained for another antibody (clone 15-2b); 15-2b antibody bound to an OEG chain with a terminal methoxy group and additional repeating EG units of 7. This binding of 15-2b was inconsistent with the previously accepted binding specificity. Additionally, quantification of anti-PEG antibodies was successfully performed, even in the presence of serum. This study highlights the significant potential of water-dispersible, antibiofouling, and post-functionalizable cello-oligosaccharide nanosheets as a solid support for ELISA immunoassay of antibodies.

Radiotherapy is one of the most common and effective clinical treatments for tumors, but how to reduce its side effects to achieve better therapeutic outcomes remains a significant challenge. As a heavy metal, bismuth (Bi) is low-cost, safe, and possesses a high X-ray attenuation coefficient, offering new opportunities to overcome these limitations. With recent advances in nanotechnology and nanomedicine, Bi-based nanoradiosensitizers have been extensively explored for enhancing tumor radiosensitization to achieve advanced diagnosis and treatment by taking advantage of their ease of preparation and modification, high stability, low cost, and excellent biocompatibility. However, the use of Bi-based nanoradiosensitizers remains in the early stages of clinical translation. In this review, we summarize the mechanisms of interaction between X-ray and Bi-based nanoradiosensitizers, discuss smart preparation and modification strategies for achieving enhanced radiotherapy sensitization effects, address material safety and biodistribution, and outline recent research advances in radiotherapy-based synergistic diagnosis and treatment. Finally, we will discuss the challenges and research priorities facing Bi-based nanoradiosensitizers to advance their clinical application development.

Cutaneous squamous cell carcinoma (cSCC) remains a formidable clinical challenge, constrained by the drawbacks of current treatments such as functional loss from surgery, radioresistance, and low adherence to protracted topical regimens. To address these issues, we designed a “photo-immuno nano-bomb” composed of polydopamine nanoparticles (PDA NPs) for co-delivering the photosensitizer chlorin e6 (Ce6) and toll-like receptor 7 agonist imiquimod (R837), thereby integrating photothermal (PTT), photodynamic (PDT), and immunotherapeutic modalities. The system utilizes π–π stacking to achieve high drug loading and stability while exhibiting a dual stimuli-responsive release profile – governed by pH-dependent surface charge alteration and photothermally triggered payload liberation – enabling more precise spatiotemporal control over combination therapy. Remarkably, the nanoformulation potently suppressed tumor cell proliferation, migration, and invasion in vitro by activating apoptotic pathways. Mechanistic studies revealed that under dual-wavelength laser irradiation (660 + 808 nm), PDA-mediated PTT enhanced cellular internalization of the nanoplatform and further augmented singlet oxygen generation, ultimately inducing mitochondrial dysfunction and cytoskeletal disintegration. This synergistic action provoked severe cellular oxidative stress and organelle damage, culminating in robust immunogenic cell death (ICD). Additionally, the platform demonstrated excellent biocompatibility, achieving complete tumor regression in vivo, outperforming all mono- and combination therapy controls. Thus, this “photo-immuno nano-bomb” multimodal strategy represents a promising therapeutic alternative for advanced cSCC, delivering superior efficacy through coordinated molecular mechanisms and minimized systemic toxicity.

Blood-contacting devices provide dual risks of thrombosis and infection in clinical applications. Conventional anticoagulants cause adverse effects and exhibit inadequate stability in hypercoagulable states. In this study, we broke away from the traditional understanding that zwitterionic hydrophilic groups dominate anti-fouling properties. We synthesized a ternary copolymer (PMLT) from MPC, LMA, and TSMA to investigate hydrophilic group proportion effects on thrombosis resistance, especially in hypercoagulable blood. Simply increasing the density of phosphocholine (PC) groups in the coating resulted in the coating losing its anticoagulant efficacy in hypercoagulable blood. Conversely, the composition-optimized PMLT-12 coating maintained a stable biomimetic bilayer structure. It demonstrated low protein adsorption and high antibacterial activity under normal conditions. Crucially, PMLT-12 retained excellent anti-thrombotic performance in challenging environments, including blood containing elevated levels of calcium ions and lipopolysaccharides (LPS), and blood from a diabetic animal model. The covalently crosslinked network mediated by TSMA concurrently enhanced the mechanical stability of the coating. This study highlights the critical role of hydrophobic–hydrophilic balance in anticoagulant efficacy against high coagulation risk, providing a novel strategy for improving blood-contacting device surfaces.

The regenerative repair of critical-sized load-bearing bone defects remains challenging in achieving stable graft fixation and timely restoration of biomechanical integrity without excessive biotherapeutics. Here, we develop a biomimetic polyamino acid/nanohydroxyapatite/high-strength/high-modulus polyvinyl alcohol fiber composite for critical-size load-bearing bone defect repair. The composites have good interfacial compatibility and cortical bone-matching mechanical strength. In vitro and in vivo studies have shown that the composites exhibit potent bioactivities and superior stability under physiological conditions and could promote osseointegration through regulating osteoblasts. More importantly, sustained biomechanical stability is attained immediately post-implantation and maintained long-term. In a rabbit model of large segmental femoral defects, osseous tissue exhibits longitudinal ingrowth along the composites, achieving bony bridging at both proximal and distal junctions with progressive remodeling. This culminates in a functionally stable bone-implant construct capable of enduring physiological loads. The current work not only develops a promising option for repairing critical-size load-bearing bone defects but also provides an idea and experimental basis for designing other functional bone biomaterials for large segmental bone defect applications.

Understanding the mechanism of interactions between synthetic polyelectrolytes and ionic matter, which are ubiquitous in living systems, such as proteins and cells, is a fundamental challenge and an important requirement for their clinical development as biomaterials and drug delivery systems. In contrast to small molecules or proteins, in which an active center or epitope largely defines the binding pattern, ionic polymers utilize a plurality of repeat units, which are capable of only weak interactions with the target individually. Although it can be expected that the effects of the chain length and cooperativity play important roles in such interactions, these effects are often overlooked in practical research. Nevertheless, preclinical experience demonstrates the existence of an activity-molar mass relationship in polyelectrolytes. Here, we focus on studying the in vitro interactions of a clinical-grade macromolecule, poly[di(carboxylatophenoxy)phosphazene] (PCPP), for which such a relationship has already been established in vivo. We found that polymers of various molar masses show different in vitro avidities to a model antigenic protein, lysozyme, with longer PCPP chains displaying lower dissociation constants and reduced entropic penalties. Higher-molar-mass polymers result in less compact complex morphologies, in which the protein is more easily accessed by the antibody. The trend of the greater in vitro activation of engineered immune cells with longer polymer chains is also observed. Results suggest that morphological and entropic benefits provided by higher-molar-mass polymers are critical in explaining previously observed in vivo trends, and these aspects should be prioritized in designing next-generation macromolecular immunoadjuvants.

Simultaneously restricting bacterial proliferation while mitigating inflammatory reactions and excessive reactive oxygen species (ROS)-mediated corneal damage during sleep represents a crucial therapeutic strategy for managing bacterial keratitis (BK). In this study, we developed micron-scale PCBT hydrogel beads for nocturnal BK treatment by integrating two classical ophthalmic drugs: tobramycin (TOB) as the antibacterial component and baicalin (BA) as the anti-inflammatory/antioxidant agent. The formation of the hydrogel beads was facilitated by the synergistic interplay between: (i) TOB solution-induced crystallization of chitosan (CS) chains and (ii) benzene-1,4-diboronic acid (1,4-BDBA) mediated ester crosslinking of polyvinyl alcohol (PVA) chains. TOB and BA were encapsulated within the hydrogel beads, with BA molecules grafted onto PVA chains via reversible phenylboronic acid ester bonds. When the PCBT hydrogel beads were applied to the inferior palpebra, mechanical friction (i.e., blink) easily transformed them into a smooth/soft paste that sustainedly released therapeutic concentrations of TOB and BA for over 10 hours in simulated BK microenvironments. Inhibition zone assays, macrophage (M_φ) polarization analyses, and ROS scavenging tests collectively demonstrated the simultaneous antibacterial, anti-inflammatory and anti-oxidative properties of the PCBT hydrogel beads. A Staphylococcus aureus (S. aureus) infected cornea model in rabbits was employed to assess the clinical therapeutic potential of the PCBT hydrogel beads against BK during sleep. The results of visual scoring, hematoxylin and eosin (H&E) staining, Masson staining, etc. indicated that the PCBT hydrogel beads exhibited superior therapeutic efficacy compared to conventional commercial eye drops, highlighting their promising application for BK treatment during nocturnal periods.

The field of tissue engineering has been an ever-evolving discipline with a principal direction of creating artificial constructs to improve biological tissue types. Constructs used in tissue engineering arise from natural compounds, synthetic polymers, or a combination of the two to generate a hybrid biomaterial with optimized characteristics. In recent years, researchers have turned to silk fibroin (SF) as a natural source for its attractive physical characteristics and tunability. Using this platform, researchers have attempted to chemically modify SF through methacrylation to further improve its mechanical properties, thus making it a more appealing candidate for bioengineering applications. To date, the two most common methacrylating agents for synthesizing methacrylated SF across literature have been glycidyl methacrylate (GMA) and methacrylic anhydride (MA), which produce SFGMA and SFMA, respectively. However, the side-by-side characterization of SFGMA and SFMA has not been well compared with respect to their synthesis reactions and resulting degrees of methacrylation (DoM). To address this, our study developed a standardized protocol for SFGMA and SFMA synthesis in an effort to systematically compare the two NMR spectra. From this protocol, our results demonstrate GMA to be the superior methacrylating agent for its reactional consistency and DoM validity.

The wound dressings currently in use have difficulties in addressing chronic inflammation and hypoxia for refractory diabetic wound prohealing. Aiming to regulate the inflammatory and hypoxic microenvironment in diabetic wounds, supramolecular reactive oxygen species (ROS)-responsive hyaluronic acid (HA) hydrogels were constructed by using salt bridge H-bonding and metal-ion coordination interactions among HA, L-arginine (Arg) and trivalent metal ions, where HA/Arg/Ce presented ROS-responsive nitric oxide (NO) and O₂ co-release behavior. In vitro and in vivo biological assays demonstrated that the lead hydrogel of HA/Arg/Ce effectively eliminated excessive ROS, polarized inflammatory M1 macrophage transition to prohealing M2 phenotype, and accelerated full-thickness skin wound healing in diabetic rats. Excitingly, single-dose treatment of HA/Arg/Ce achieved high-performance diabetic wound healing, including optimal re-epithelialization and dermis regeneration, 82.3% collagen deposition, ∼2.5-fold hair follicles and ∼3.0-fold skin tensile strength compared to Tegaderm. Significantly, this work provides a versatile strategy for the preparation of supramolecular HA hydrogels with long-acting NO/O₂ co-release properties for potential translation in chronic diabetic wound dressings.

Concerns over in vivo Gd(III) retention have recently prompted the development of Gd(III)-based contrast agents (GBCAs) with high-relaxivity and stability. This work describes the synthesis of a novel modular and enantiomerically pure chelator, (R,R,R)-Bn₃-PCTAZA 8 allowing modification via Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC). Two zwitterionic GBCAs, Gd-SB₃-PCTA 11a and Gd-NOx₃-PCTA 12a, were prepared by CuAAC and analysed for important physicochemical properties and complex stability. Both zwitterionic complexes have improved kinetic inertness compared to the clinically relevant GBCA gadopiclenol 3. In addition, Gd-SB₃-PCTA 11a revealed an 18% increase in relaxivity (r₁) compared to gadopiclenol 3. Gd-NOx₃-PCTA 12a, has a slightly lower relaxivity but the highest kinetic stability among all complexes tested. Both agents maintain high relaxivity at clinically relevant magnetic field strengths (1.4 T and 7 T) and have high inertness under transmetallation conditions, acidic conditions and in human serum. These favourable characteristics are due to enhanced second-sphere hydration of the kosmotropic periphery of the complexes. Gd-SB₃-PCTA 11a revealed a significantly reduced retention in mice kidneys compared to gadopiclenol 3. The zwitterionic GBCAs Gd-SB₃-PCTA 11a and Gd-NOx₃-PCTA 12a are thus promising candidates for the development of next-generation contrast agents for magnetic resonance imaging (MRI).