Biomaterials最新文献

{"title":"Spatiotemporal controls of neutrophil extracellular traps boosts neutrophils immunotherapy efficiency against solid tumors","authors":"Lingxiao Jin ,&nbsp;Liang Chen ,&nbsp;Yucheng Xue ,&nbsp;Keye Chen ,&nbsp;Shixin Chen ,&nbsp;Kelei Wang ,&nbsp;Fangqian Wang ,&nbsp;Guoxin Qu ,&nbsp;Zhenxuan Shao ,&nbsp;Shenzhi Zhao ,&nbsp;Haochen Mou ,&nbsp;Hao Zhou ,&nbsp;Zengjie Zhang ,&nbsp;Xiayu Hu ,&nbsp;Jiangchu Lei ,&nbsp;Fanglu Chen ,&nbsp;JianBin Xu ,&nbsp;Peng Zhang ,&nbsp;Binghao Li","doi":"10.1016/j.biomaterials.2026.124012","DOIUrl":"10.1016/j.biomaterials.2026.124012","url":null,"abstract":"<div><div>Neutrophils have emerged as promising candidates for next-generation immunotherapies against solid tumors. However, the physical barrier formed by tumor-induced neutrophil extracellular traps (NETs) significantly restricts the migration and infiltration of circulating immune cells, thereby limiting their anti-tumor efficacy. This study demonstrated tumors driven NET formation.</div><div>within recruited neutrophils via the Transforming Growth Factor Beta (TGFβ) signaling pathway. Therefore, a neutrophil-arming nanoplatform (NE@LTT@DNase1) was developed to enable neutrophils to degrade NETs while preserving their innate immune functions. Mechanistically, NE@LTT@DNase1 exerts dual therapeutic effects: (i) enzymatic degradation of pre-existing NETs via neutrophil surface-anchored DNase1 and (ii) spatiotemporal suppression of NETosis via endogenous lysine-trypotophan-threonine peptide (LTT) fragmentation in a reactive oxygen species-dependent manner. Data show that NE@LTT@DNase1 treatment was associated with increased infiltration of NK cells and T cells, as well as a shift of neutrophils and macrophages toward an anti-tumor polarization, collectively contributing to the reversal of the immunosuppressive tumor microenvironment (TME). In combination with anti-Programmed Death-1 (anti-PD-1) therapy, the NE@LTT@DNase1-based immunotherapy strategy resulted in a 74 % reduction in tumor burden and prolonged median survival by 61 % in tumor-bearing mice. Overall, these findings established a next-generation therapeutic paradigm for advanced neutrophil-based immunotherapy (NBI).</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124012"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-activated metal-polyphenol nanodroplets for tumor cuproptosis","authors":"Ning Cong ,&nbsp;Lu Guo ,&nbsp;Xiaoxuan Wang ,&nbsp;Yading Zhao ,&nbsp;Ting Zhao ,&nbsp;Shuting Huang ,&nbsp;Rui Liu ,&nbsp;Song Ning ,&nbsp;Xiaoying Zhou ,&nbsp;Suyun Li ,&nbsp;Yuye Fu ,&nbsp;Jie Li","doi":"10.1016/j.biomaterials.2026.124013","DOIUrl":"10.1016/j.biomaterials.2026.124013","url":null,"abstract":"<div><div>Cuproptosis is a novel form of cell death that relies on mitochondrial metabolism and has opened up new avenues for tumor therapy. However, resistance to cuproptosis in tumors can arise from several factors, such as their reliance on aerobic glycolysis, the high-glutathione (GSH) environment, and inefficient copper (Cu) delivery. In this study, we developed shell-core nanodroplets (NDs) approximately 280 nm in diameter, named Cu-EGCG-SHK-NDs. These NDs are composed of a liquid-gas phase-change perfluorohexane core and a carboxymethyl chitosan shell, loaded with the glycolytic inhibitor shikonin (SHK) and coated with Cu-complexed epigallocatechin gallate (Cu-EGCG), enabling targeted delivery through ultrasound (US)-targeted microbubble destruction (UTMD). The dual responsiveness of NDs to both US and pH enables precise drug release and efficient intracellular uptake. In addition, the US response enhances contrast-enhanced US imaging and triggers the generation of reactive oxygen species, subsequently depleting GSH. Both <em>in vitr</em><em>o</em> and <em>in vivo</em> experiments confirm that Cu-EGCG-SHK-NDs possess excellent biocompatibility. Combined with UTMD, they can efficiently co-deliver Cu and SHK into tumour cells, inhibit glycolytic metabolism, and significantly reduce intracellular GSH levels. This synergistic mechanism enhances cuproptosis induction and achieves effective tumour growth inhibition.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124013"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalable DNA nano-adjuvant elicits robust lung-resident memory immunity against pneumonic plague","authors":"Shengnan Fu ,&nbsp;Zhixin Li ,&nbsp;Zhe Yin ,&nbsp;Xi Zhang ,&nbsp;Xiaolin Song ,&nbsp;Lingfei Hu ,&nbsp;Dongsheng Zhou ,&nbsp;Xin Su ,&nbsp;Chenxi Dai","doi":"10.1016/j.biomaterials.2026.124009","DOIUrl":"10.1016/j.biomaterials.2026.124009","url":null,"abstract":"<div><div>Pneumonic plague, caused by <em>Yersinia pestis</em>, remains a deadly threat due to its high mortality and rapid progression. In our previous study, <em>Yersinia pestis</em> antigens formulated with CpG oligodeoxynucleotides show great potential against pneumonic plague, but these agonists display low TLR9 affinity, poor stability, limited cellular uptake, and weak induction of tissue-resident memory immunity. Here, we introduce AdjCRU, a cruciform DNA nano-adjuvant built on a four-way junction with each arm presenting looped CpG motifs (LoDNA) for TLR9 engagement. Guided by computational design and molecular dynamics simulations, the four-way junction is chosen over other nanostructures for superior TLR9 binding. AdjCRU is nuclease-resistant, prepared by one-step annealing of four single-stranded oligonucleotides. When administered via aerosolized intratracheal inoculation alongside <em>Yersinia pestis</em> recombinant antigen rV10, AdjCRU is effectively internalized into lysosomes of antigen-presenting cell (APC), inducing markedly enhanced APC maturation, germinal center reaction, systemic and mucosal antibody titers, and T/B cell activation. Notably, rV10+AdjCRU drives robust lung-resident memory T/B cell immunity, and significantly improves survival by 40 % over free LoDNA in a lethal pneumonic plague mouse model. By integrating programmability, biocompatibility, and enhanced TLR9 stimulation into a single, modular platform, AdjCRU offers a versatile strategy for next-generation mucosal adjuvants against respiratory pathogens.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124009"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAK modulates immune response and fibroblast activation in biomaterial-induced fibrosis","authors":"Marc A. Fernández-Yagüe ,&nbsp;Graham F. Barber ,&nbsp;Aránzazu del Campo ,&nbsp;Andrés J. García","doi":"10.1016/j.biomaterials.2026.124010","DOIUrl":"10.1016/j.biomaterials.2026.124010","url":null,"abstract":"<div><div>Fibrotic capsule formation remains a major barrier in the clinical performance of biomedical implants. Here, we demonstrate that synthetic hydrogels mimicking the mechanical properties of fibrotic tissue trigger stromal cell activation and immune remodeling via focal adhesion kinase (FAK)-mediated mechanotransduction. Using a mechanically tunable poly(ethylene glycol) hydrogel platform and subcutaneous implantation in mice, we show that pharmacological inhibition of FAK activity significantly reduces α-smooth muscle actin (α-SMA)-positive myofibroblast activation, collagen I deposition, and fibrotic capsule thickness in a hydrogel stiffness-dependent manner. Flow cytometry and cytokine profiling revealed that FAK inhibition alters the fibrotic niche by reducing CD163-positive M2c macrophages and significantly downregulating pro-fibrotic cytokines including IL-6, and VEGF, while transiently increasing regulatory T cells and elevating IL-10 levels. Importantly, these changes occurred without parallel increases in canonical pro-inflammatory cytokines, indicating selective modulation rather than global immune suppression or activation. These findings position FAK as a central hub translating mechanical cues into coordinated stromal and immune responses. Targeting FAK mechanotransduction may provide a therapeutic strategy to mitigate foreign body responses and improve implant integration across regenerative applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124010"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the HMnO2 nanoparticles as the DNA injury amplifier to improve the OXA-based trans-artery infusion chemotherapy","authors":"Xianting Sun ,&nbsp;Cai Feng ,&nbsp;Zongling Xiong ,&nbsp;Yifei Yang ,&nbsp;Hao Zhou ,&nbsp;Tianming Wang ,&nbsp;Xiaofen Wang ,&nbsp;Shulin Liu ,&nbsp;Sai Li ,&nbsp;Peng Lei ,&nbsp;Liangrong Shi ,&nbsp;Weihua Liao","doi":"10.1016/j.biomaterials.2026.123993","DOIUrl":"10.1016/j.biomaterials.2026.123993","url":null,"abstract":"<div><div>Oxaliplatin (OXA) serves as a key chemotherapeutic agent in trans-arterial infusion chemotherapy (TAIC) for liver cancer. However, its clinical efficacy is frequently limited by several factors: suboptimal tumor uptake, systemic detoxification mediated by glutathione (GSH), and the activation of cellular DNA repair mechanisms. Herein, we present a hollow MnO₂ nanoparticle loaded with OXA, the PEI-HMnO₂@OXA, to improve the TAIC effect of OXA. The acidic tumor microenvironment facilitated the release of OXA and triggered PEI-HMnO₂ to generate free radicals. When coupled with GSH depletion, this cascade culminated in significant DNA damage. Moreover, the PEI-HMnO₂ showed a synergistic effect with OXA by blocking multiple DNA repair genes. On the other hand, by leveraging the enhanced permeability and retention effect of the nano-sized structure, 10–100 times greater tumor uptake and a more pronounced inhibitory effect by TAIC are achieved compared with intravenous or single-drug treatment. Meanwhile, the PEI-HMnO₂@OXA enabled real-time MRI monitoring of drug distribution and tumor state, facilitating the treatment guidance. Comprehensive experiments using different cell lines, mouse and rabbit models, and patient-derived HCC OXA-sensitive/resistant organoids were conducted to clarify the tumor-inhibiting effects of PEI-HMnO₂@OXA, providing novel insights into cancer management.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 123993"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Near-infrared orthogonal excitation lanthanide theranostic nanoplatform for NIR-II-L imaging-guided photodynamic therapy via synergistical pyroptosis and apoptosis pathway","authors":"Jialing Zhou ,&nbsp;Jiang Ming ,&nbsp;Zhenfeng Yu ,&nbsp;Zhihua Wang ,&nbsp;Wenlin Li ,&nbsp;Ahmed Mohamed El-Toni ,&nbsp;Aliyah Almomen ,&nbsp;Aibin Liang ,&nbsp;Yong Fan ,&nbsp;Fan Zhang","doi":"10.1016/j.biomaterials.2026.123994","DOIUrl":"10.1016/j.biomaterials.2026.123994","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) that induces pyroptosis at the cell membrane has emerged as a promising paradigm for cancer immunotherapy. However, the rapid and precise induction of pyroptosis remains a significant challenge. To address this, we developed a near-infrared orthogonal excitation lanthanide theranostic nanoplatform based on lanthanide doped nanoparticles conjugated with curcumin (CUR) and cyclo(RGD-DPhe-K) peptide (LnNP@CUR-RGD). This platform enables deep-tissue, NIR-II-L imaging-guided PDT that concurrently initiates both pyroptosis and apoptosis. Upon 808 nm excitation, fluorescence at 1530 nm from LnNP@CUR-RGD allows for real-time in vivo tracking and monitoring of its localization to the cell membrane or lysosome. After subsequently switching to 940 nm excitation, the produced 362 nm emission activates CUR to generate singlet oxygen (¹O₂). This process initiates a dual-death mechanism: cell membrane-involved pyroptosis and lysosome-involved apoptosis, which synergistically potentiate the anti-tumor immune response. Notably, this nanoplatform achieves efficient antitumor therapy within 15 min of systemic administration, a significant acceleration compared to the 6 h required for conventional apoptosis-based PDT. This work demonstrates the considerable potential of NIR-light-triggered, targeted theranostic platforms for precise imaging-guided cancer therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 123994"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling the T cell response to polypropylene mesh in a non-human primate sacrocolpopexy model","authors":"Srividya Kottapalli ,&nbsp;Marrisa Therriault ,&nbsp;Rui Liang ,&nbsp;Malini Harinath ,&nbsp;Gabby King ,&nbsp;Pamela A. Moalli ,&nbsp;Amanda Artsen","doi":"10.1016/j.biomaterials.2026.124008","DOIUrl":"10.1016/j.biomaterials.2026.124008","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Polypropylene mesh (PPM) improves anatomic outcomes in pelvic organ prolapse (POP) repair, yet complications—most commonly pain and mesh exposure—occur in ∼10 % of cases. Clinically, meshes that are implanted flat often demonstrate striking deformation at explanation, including pore collapse and wrinkling. Both computational models and &lt;em&gt;in vivo&lt;/em&gt; studies confirm that mesh geometry changes substantially after tensioning during prolapse repair. Although T cells have been implicated in mesh-related complications, the specific impact of mesh deformation on adaptive immunity is not fully understood.&lt;/div&gt;&lt;div&gt;To address this gap, a lightweight PPM (Restorelle) was implanted in nonhuman primates either in its flat configuration (stable, R0) or engineered into two progressively deformed geometries: R45 (unstable: pore collapsed) and RD (predeformed: pore collapsed + wrinkled). Sham-operated animals served as controls. Twelve weeks post-implantation, mesh–tissue complexes were analyzed to quantify T-cell phenotypes, tissue remodeling, and downstream healing outcomes. Findings were integrated with a comparative proteomic analysis of flat versus deformed human mesh explants.&lt;/div&gt;&lt;div&gt;Mesh burden increased stepwise with deformation (R0 &lt; R45 &lt; RD). Deformation amplified T-cell infiltration within the vaginal adventitia, with helper T cells dominating and cytotoxic T cells contributing minimally. T&lt;sub&gt;regs&lt;/sub&gt; were enriched in the moderately deformed R45 group—consistent with injury resolution—but were markedly reduced in RD, indicating a shift toward chronic, non-resolving inflammation. Whereas flat meshes maintained organized collagen and physiologic fibrotic encapsulation, deformed meshes—particularly RD—exhibited loss of organized ECM, increased fibroblast-driven remodeling, and elevated fibroblast growth factor-2 (FGF-2). Cytokine profiling revealed increased IL-1β and CXCL12 across all mesh groups, but RD uniquely showed suppression of Th2 cytokines (IL-4, IL-5), a signature of impaired immune resolution.&lt;/div&gt;&lt;div&gt;Human explants mirrored key primate findings: CD99, a marker of T-cell trafficking and persistent activation, was elevated in specimens from patients with complications, while CD84, which mediates T:B-cell interactions and memory formation, was reduced—suggesting repetitive T-cell activation without durable immune regulation.&lt;/div&gt;&lt;div&gt;Together, these results demonstrate that increasing mesh deformation drives a shift from a Th2/Treg-dominant, pro-resolution immune response toward chronic inflammation characterized by persistent T-cell activation and fibroblast-mediated ECM disruption. This work directly links mesh geometry–induced mechanical stress to adaptive immune dysregulation and disordered collagen remodeling and validates these signatures in human specimens. The findings highlight actionable opportunities for geometry-preserving mesh designs and targeted T-cell–directed immunomodulation to prevent complicati","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124008"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shaping mesenchymal stem cell fate with a two-dimensional covalent triazine framework for calmodulin modulation","authors":"Lei Wang ,&nbsp;Boyu Zheng ,&nbsp;Maryam Salahvarzi ,&nbsp;Yi-An Yang ,&nbsp;Yan Nie ,&nbsp;Philip Nickl ,&nbsp;Mathias Dimde ,&nbsp;Kai Ludwig ,&nbsp;Xun Xu ,&nbsp;Yiduo Zhou ,&nbsp;Junyao Zhang ,&nbsp;Weiwei Wang ,&nbsp;Xiao Ling ,&nbsp;Xingjun Qin ,&nbsp;Lukas Prantl ,&nbsp;Oliver Felthaus ,&nbsp;Wenzhong Li ,&nbsp;Mohsen Adeli ,&nbsp;Nan Ma","doi":"10.1016/j.biomaterials.2026.123997","DOIUrl":"10.1016/j.biomaterials.2026.123997","url":null,"abstract":"<div><div>Calmodulin (CaM) is a central calcium sensor and signaling hub that critically governs stem cell fate. However, directly intracellular modulation of CaM remains challenging due to its activity is tightly coupled to finely balanced calcium homeostasis, and conventional chemicals or biomaterials have limited ability to access or target it. Here, we introduce a novel two-dimensional, porous, covalent triazine-based framework, CTF-Ca, synthesized under ambient conditions, that offers a new strategy for intracellular CaM regulation. Unlike conventional approaches, CTF-Ca bypasses membrane calcium channels, enabling direct calcium influx into mesenchymal stem cells (MSCs) and triggering robust, sustained activation of the Ca²⁺/CaM signaling pathway. This activation markedly enhances osteogenic differentiation in MSCs. Remarkably, CTF-Ca also compensates for suppressed CaM function, restoring osteogenic potential in MSCs even under CaM-inhibited conditions. This compensatory effect was further demonstrated in C2C12 myogenic progenitor cells, a skeletal muscle model characterized with high endogenous CaM expression, where CTF-Ca rescued myotube formation in CaM deficient cells, underscoring its broad applicability. Together, these findings establish CTF-Ca as an effective 2D material for direct intracellular modulation of CaM, offers a promising new tool for regulating stem and progenitor cells fate.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 123997"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cascade-enhanced Pt nanozyme platform anchored on microgels for effective lactate depletion and EndoMT attenuation post-myocardial infarction","authors":"Liang Song ,&nbsp;Yongyuan Kang ,&nbsp;Pai Peng ,&nbsp;Qiaoxuan Wang ,&nbsp;Liyin Shen ,&nbsp;Jinyue Zhang ,&nbsp;Yang Zhu ,&nbsp;Changyou Gao","doi":"10.1016/j.biomaterials.2026.124005","DOIUrl":"10.1016/j.biomaterials.2026.124005","url":null,"abstract":"<div><div>Myocardial infarction (MI) often leads to excessive lactate accumulation, which drives endothelial-to-mesenchymal transition (EndoMT) and subsequent myocardial fibrosis. Lactate oxidase (LOx) has been identified as a potential therapeutic enzyme capable of degrading excess lactate. However, the hypoxic environment characteristic of MI diminishes the catalytic efficiency of LOx. In this study, platinum (Pt) nanozymes with catalase-like (CAT-like) activity were introduced, which catalyzed the decomposition of hydrogen peroxide (H₂O₂) to generate oxygen (O₂), thereby enhancing LOx activity. A strategy involving microgel-anchored LOx-loaded Pt nanozymes (PPtL@MGs) was proposed by loading LOx-loaded Pt nanozymes to microgels, enabling targeted delivery and prolonged retention within the infarcted myocardium. The PPtL@MGs exhibited robust CAT-like activity and effectively enhanced LOx-mediated lactate clearance <em>in vitro</em>, thereby alleviating hypoxia/H₂O₂-induced EndoMT in HUVECs. Consequently, it promoted vascular endothelial cadherin (VE-cadherin) expression, suppressed fibroblast-specific protein 1 (FSP1), reduced myocardial fibrosis, and significantly improved cardiac function <em>in vivo</em>. These results demonstrate the potential of this microgel-anchored nanozyme system, which enables cascade-enhanced lactate modulation through O₂ generation and effective lactate clearance, thereby alleviating the MI-induced fibrosis and dysfunction.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124005"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methionine-depleting engineered probiotics promote PD-L1 antibody immunotherapy by activating the STING pathway","authors":"Tiantian Sun ,&nbsp;Qiushuang Zhang ,&nbsp;Yicong Dai ,&nbsp;Yuhan Liu ,&nbsp;Xucong Teng ,&nbsp;Jinghong Li","doi":"10.1016/j.biomaterials.2026.124015","DOIUrl":"10.1016/j.biomaterials.2026.124015","url":null,"abstract":"<div><div>The metabolic differences between tumor cells and normal tissue cells offer potential targets for therapeutic intervention. For instance, compared to normal tissues, tumor cells exhibit a significantly higher dependency on methionine. However, current strategies for methionine restriction have limited clinical applicability due to systemic toxicity, poor patient compliance, and insufficient tumor targeting. In this study, we developed an engineered probiotic, Met-EcN, which is able to achieve targeted consumption of methionine within the tumor microenvironment. In the B16–F10 melanoma mouse model, the combination of Met-EcN and anti-PD-L1 antibody led to a 63 % increase in the tumor inhibition rate compared to anti-PD-L1 treatment alone, as well as a 50 % improvement in mouse survival rates. Additionally, this combination significantly enhanced T cell infiltration and activation. In the MC-38 colon cancer model, treatment with Met-EcN alongside anti-PD-L1 antibody inhibited tumor growth by 84.6 %, leading to complete regression of tumors in 80 % of the mice. The depletion of methionine levels by Met-EcN leads to a reduction in methylation levels within tumor cells, which facilitates the dissociation of cGAS protein from chromatin and activates the STING signaling pathway, thereby triggering an innate immune response. This study provides a novel therapeutic approach for overcoming tumor immune resistance.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 124015"},"PeriodicalIF":12.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}