Journal of Materials Chemistry B最新文献

Lung cancer remains one of the most lethal malignancies worldwide. Despite recent advances, current immunotherapies are often limited by the immunosuppressive tumor microenvironment and insufficient local immune activation. Herein, we report the development of an injectable dual-adjuvant hydrogel (CpG@Mn-Gel) formed by coordinating phosphate-functionalized hyaluronic acid with Mn²⁺ ions. This hydrogel enables in situ gelation and sustained release of both CpG oligodeoxynucleotides, Toll-like receptor 9 (TLR9) agonists, and Mn²⁺, a stimulator of the STING pathway, thereby providing spatiotemporally controlled immune activation. In a metastatic lung cancer model, CpG@Mn-Gel significantly inhibited tumor progression, reduced pulmonary metastases, and prolonged overall survival. Mechanistic studies revealed that CpG@Mn-Gel enhanced dendritic cell maturation in draining lymph nodes, promoted CD8⁺ T cell infiltration into tumor tissues, and upregulated local expression of effector cytokines including IFN-γ and TNF-α. Moreover, systemic immune memory was established, as evidenced by an increased proportion of CD44⁺CD62L⁻ effector memory T cells in the spleen. These results demonstrate that combining CpG and Mn²⁺ within a localized hydrogel matrix can synergistically activate antitumor immunity, offering a promising platform for lung cancer immunotherapy.

Current biocompatibility assessment paradigms inadequately predict hemoglobin–material interactions, limiting the rational design of blood-contacting biomedical devices. We developed a hemoglobin sensitivity index (HSI), a predictive mathematical framework integrating ten mechanistically derived parameters, namely binding thermodynamics, electrostatic interactions, hydrophobic forces, size-dependent diffusion kinetics, morphological effects, surface reactivity, oxidative stress generation, temporal stability, protein corona dynamics, and mechanical stress responses, through validated computational models. Each parameter was mathematically normalized using physical scaling laws and weighted through multi-objective optimization across ten biomedical applications. We computationally evaluated 25 materials spanning organic polymers, inorganic nanomaterials, and hybrid systems through literature results and predictive modeling. The HSI demonstrated exceptional theoretical predictive accuracy with a coefficient of determination (R²) of 0.943 and a root mean square error of 0.087 when validated against computational predictions and literature-derived cytotoxicity databases containing 1247 material-application pairs. Machine learning-enhanced parameter weighting revealed reactive oxygen species generation and binding affinity as dominant contributors with predicted weights of 0.247 ± 0.032 and 0.182 ± 0.023, respectively. Polymer-based material classes, including PEG polymers, exhibited predicted HSI values of 0.45–0.52, while carbon materials showed predicted risk profiles of 3.12–7.23. Application-specific optimization reduced the average predicted HSI by 67% compared to conventional designs. This HSI framework establishes the first quantitative, mechanistically grounded computational platform for predicting hemoglobin–material interactions, enabling rational biocompatible material design and supporting regulatory harmonization for accelerated clinical translation.

Liposarcoma is a challenging soft tissue sarcoma where the tumor microenvironment (TME) critically drives progression, invasion, and therapy resistance. Conventional preclinical models, particularly 2D cultures, fail to recapitulate this complex interplay, hindering the development of effective therapies. To address this, we developed and validated a novel 3D bioprinted liposarcoma model that integrates human liposarcoma cells, cancer-associated fibroblasts (CAFs), and human umbilical vein endothelial cells within a biomimetic collagen/hyaluronic acid composite hydrogel. This engineered TME model successfully reproduced key in vivo features, including a soft tissue mechanical environment, CAF activation, and angiogenic network formation. Compared to 2D or 3D mono-cultures, the complete TME significantly promoted liposarcoma cell proliferation and invasion. Transcriptomic analysis revealed that the TME induces profound functional reprogramming. Liposarcoma cells were driven toward an aggressive, epithelial–mesenchymal transition like phenotype via activation of TGF-β and other hallmark cancer pathways, while CAFs were activated into a pro-inflammatory, highly proliferative state. Critically, the 3D TME model conferred significant resistance to the standard chemotherapeutic agent, doxorubicin, which confirmed that this chemoresistance is mediated by a combination of physical barriers arising from cell–matrix remodeling and protective paracrine signaling from the stromal cells. In conclusion, our 3D bioprinted TME model provides a physiologically relevant and robust preclinical platform. It serves as a powerful tool for investigating the molecular mechanisms of TME-driven liposarcoma progression and chemoresistance, offering a new paradigm for the high-throughput screening of novel therapeutics that target tumor–stroma interactions.

To address the systemic toxicity of the chemotherapeutic drug doxorubicin (DOX) and improve its targeted delivery efficiency for leukemia treatment, this study developed a folic acid (FA) receptor-targeted, photo-responsive nanodrug delivery system. The system was examined for its in vitro and in vivo antitumor performance against the K562 leukemia cell line. The core of this platform is a mesoporous covalent organic framework (COF), THPP_TK, synthesized through the following steps: (1) preparation of a singlet oxygen (¹O₂)-sensitive thioketal (TK) linker; (2) formation of the THPP_TK COF via esterification between TK and 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (THPP); (3) surface modification of THPP_TK using FA-conjugated polyethylene glycol (FA-PEG), acting as both a reaction terminator and hydrophilic coating; (4) loading of DOX into the COF mesopores to obtain the final nanodrug DOX@THPP_TK-PEG-FA. This system employs a dual photoactivation process: under 660 nm laser irradiation, the THPP component generates ¹O₂ for photodynamic therapy (PDT), while also initiating cleavage of the TK linker to enable controlled release of DOX for chemotherapy (CT). This cascade mechanism strengthens the overall antitumor response. Studies in a Balb/c nude mouse subcutaneous xenograft model using K562 cells confirmed the nanosystem's strong tumor-targeting ability, notable in vitro and in vivo antitumor activity, and reduced DOX-associated systemic toxicity.

Correction for ‘Tumor-targeting polymer nanohybrids with amplified ROS generation for combined photodynamic and chemodynamic therapy’ by Xiaodan Chen et al., J. Mater. Chem. B, 2024, 12, 1296–1306, https://doi.org/10.1039/D3TB02341A.

The blood compatibility of blood-contacting catheters is frequently challenged by fibrinogen, platelets, and bacteria. Adhesion and denaturation of any of these can lead to device failure and damage. Although passive antifouling coatings effectively inhibit the adhesion of proteins and platelets, their performance may degrade in the complex blood environment. Here, we propose an antifouling coating based on an active–passive synergistic strategy that mimics both cell membrane and endothelial functions. A copolymer PMLA layer simulates the cell membrane structure, providing passive antifouling properties and effectively inhibiting coagulation at an early stage. Additionally, Cu²⁺ ions are introduced into the coating interface via EGCG, catalyzing the release of nitric oxide (NO) to impart active antifouling ability to the coating. This combined strategy of endothelial mimicry and cell membrane simulation effectively suppresses platelet and protein adhesion and endows the coating with excellent antibacterial properties. Results from ex vivo thrombogenicity studies demonstrate that the proposed active/passive strategy effectively prevents thrombosis formation, offering a promising approach for the functional modification of blood-contacting catheter materials.

CD200, an immunoregulatory glycoprotein of the immunoglobulin superfamily, suppresses inflammatory signaling by engaging its receptor CD200R, which is predominantly expressed on myeloid cells. To enhance the immune-evading properties of viral vectors, we engineered lentiviral particles displaying the CD200 ectodomain (CD200ED) to exploit anti-inflammatory response and phagocytosis resistance. A fusion gene encoding the mouse CD200 ectodomain and core streptavidin (CD200ED-coreSA) was cloned into the pET-30a(+) plasmid, expressed in E. coli Lemo21(DE3), and purified via immobilized metal affinity chromatography (IMAC). Successful protein assembly was confirmed by SDS-PAGE and western blot. Biotinylated VSV-G pseudotyped lentiviral vectors, encoding a green fluorescent protein reporter, were functionalized with CD200ED-coreSA. When exposed to murine J774A.1 macrophages, CD200ED-modified lentiviruses significantly reduced pro-inflammatory cytokine production - evidenced by 47.1% decrease in TNF-α and 55% decrease in IL-6 - compared to unmodified controls. Additionally, CD200ED anchoring reduced macrophage phagocytosis of lentiviral particles by 25%. These findings demonstrate that CD200-tethering confers dual anti-inflammatory and phagocytosis resistance capabilities to viral vectors, offering a promising strategy to improve gene delivery efficiency in inflammatory environments.

Live cell tracking is a critical technical requirement across regenerative medicine, disease mechanism research, immunotherapy, and diagnosis. Rapid, wash-free labeling with multimodal imaging capabilities would greatly facilitate subsequent in vivo applications. Herein, we report a general, wash-free, and rapid live cell labeling strategy using an ¹⁸F-radiolabeled near-infrared fluorescent Bodipy dye. In extracellular solution, the dye self-assembles into fluorescence-quenched ¹⁸F-positron emitting nanoparticles, while upon cellular endocytosis, the nanoparticles disassemble, triggering a >170-fold fluorescence “turn-on” that eliminates background interference without washing. The integration of fluorescence and positron emission tomography (PET) at the molecular level enables accurate in vivo cell tracking via whole-body PET scanning and local fluorescence imaging. We validated the strategy by labeling cancer cells for tracking tumor metastatic circulation and red blood cells for imaging intracranial hemorrhage (stroke), demonstrating its broad utility for in vivo cell-tracking applications.

Experimental autoimmune uveitis (EAU) is a widely used model for non-infectious uveitis (NIU), a sight-threatening autoimmune ocular disease. Although glucocorticoids remain the first-line therapy, their short half-life and frequent administration increase the risk of systemic and ocular side effects. Here, we report the development of microenvironment-responsive hydrogels with drug-loaded microspheres for sustained dexamethasone acetate release: dexamethasone acetate-loaded microspheres (DAMS) and polyethylene glycol (PEG) hydrogel-encapsulated microspheres (DAMS@Gel). Poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated and subsequently embedded in pH-responsive and injectable hydrogels formed via Schiff base crosslinking. The materials were then thoroughly characterized. In vitro, both DAMS and DAMS@Gel exhibited excellent biocompatibility with retinal pigment epithelial (ARPE-19) cells, as confirmed by reactive oxygen species (ROS), apoptosis, cell cycle, and cytotoxicity assays. In vivo safety was verified through subconjunctival injection in rabbits. In the rat EAU model, intravitreal administration of DAMS and DAMS@Gel significantly alleviated ocular inflammation, as evidenced by ocular inflammatory symptom observations, fundus imaging, histopathological examination, and decreased glial activation. This study demonstrated that the DAMS and DAMS@Gel drug delivery systems were successfully established and exhibited sustained release properties and stable characteristics. In vitro and in vivo assays indicated that the biological materials had excellent biocompatibility. In addition, both DAMS and DAMS@Gel exerted therapeutic effects on the EAU model rats, and intraocular inflammation was reduced. This research provides a theoretical foundation for the treatment of uveitis with DAMS and DAMS@Gel.

The development of safe, effective preservatives that avoid fostering drug resistance remains a significant challenge for prolonging the freshness of fruits and vegetables. Addressing this, we synthesized two distinct carbon-based phosphatase nanozymes (CNPs) from methyl red dye using L-cysteine (L-Cys) or N-acetyl-L-cysteine (NAC) as sulfur-containing precursors. These CNPs exhibited potent, broad-spectrum antimicrobial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus epidermidis, with a minimum inhibitory concentration (MIC) of 125–250 µg mL⁻¹. As opposed to the most conventional reactive oxygen species (ROS)-based antimicrobial mechanism, the present work proposed a mechanism based on robust phosphatase-mimetic activity. It catalyzes the non-specific dephosphorylation of phosphate groups in the bacterial outer membrane and cell wall, and pioneers the development of antimicrobial agents against Gram-negative bacteria. The L-Cys-derived CNPs demonstrated superior phosphatase activity and correspondingly stronger antibacterial efficacy. At the MIC, this nanozyme effectively prevented mold growth on tomatoes for 14 days, significantly extending their shelf life. This work highlights the promise of carbon phosphatase nanozymes as a novel class of potential resistance-resistant antimicrobial agents for agricultural applications.