Pub Date : 2026-02-03DOI: 10.1016/j.mtbio.2026.102892
Zelong Jiang , Hong Huang , Mengqi Zhang , Feng Lin , Guchun Qin , Niqiang Zhou , Guanhua Qiu , Jie Chen , Duo Wang , Yunxi Huang , Chang Zhao
Magnetic hyperthermia therapy (MHT) has emerged as a promising anti-cancer strategy due to its precise spatial controllability and immune-activating effects. However, tumor cells can rapidly develop thermotolerance through the upregulation of heat shock proteins (HSPs), activation of the NF-κB signaling pathway, and recruitment of immunosuppressive cells, etc. Herein, we design a tumor cell membrane coated H2S-releasing magnetic nanoplatform (CmMN@ADT) to overcome this resistance. This nanoplatform was synthesized by coordinating Fe3O4 nanoparticles with 1,3,5-benzenetricarboxylic acid (BTC) to form a magnetic metal organic framework (Fe3O4@MIL-100, MN), which was subsequently loaded with the H2S donor ADT-OH and coated with tumor cell membranes for homotypic targeting. Upon exposure to an alternating magnetic field (AMF), the Fe3O4@MIL-100 core enables localized hyperthermia, while acidic tumor microenvironment triggers ADT-OH release for sustained H2S generation. The released H2S enhances tumor cell sensitivity to hyperthermia by inhibiting NF-κB activation and downregulating HSP expression. Suprisingly, H2S can also augment the MN induced ferroptosis. In vitro and in vivo studies have demonstrated that CmMN@ADT effectively induces tumor ablation and elicits potent anti-tumor immune responses, ultimately achieving the inhibition of the growth of both primary and metastatic tumors. Collectively, this study presents a novel H2S driven magnetic MOF nanoplatform that achieves dual mode synergy between H2S Augmented MHT and ferroptosis, providing a mechanistically guided strategy to overcome tumor thermotolerance and achieve durable tumor suppression.
{"title":"A biomimetic magnetic MOF-based nanoplatform for H2S-mediated thermal re-sensitization and immune reprogramming in multimodal hyperthermia therapy","authors":"Zelong Jiang , Hong Huang , Mengqi Zhang , Feng Lin , Guchun Qin , Niqiang Zhou , Guanhua Qiu , Jie Chen , Duo Wang , Yunxi Huang , Chang Zhao","doi":"10.1016/j.mtbio.2026.102892","DOIUrl":"10.1016/j.mtbio.2026.102892","url":null,"abstract":"<div><div>Magnetic hyperthermia therapy (MHT) has emerged as a promising anti-cancer strategy due to its precise spatial controllability and immune-activating effects. However, tumor cells can rapidly develop thermotolerance through the upregulation of heat shock proteins (HSPs), activation of the NF-κB signaling pathway, and recruitment of immunosuppressive cells, etc. Herein, we design a tumor cell membrane coated H<sub>2</sub>S-releasing magnetic nanoplatform (CmMN@ADT) to overcome this resistance. This nanoplatform was synthesized by coordinating Fe<sub>3</sub>O<sub>4</sub> nanoparticles with 1,3,5-benzenetricarboxylic acid (BTC) to form a magnetic metal organic framework (Fe<sub>3</sub>O<sub>4</sub>@MIL-100, MN), which was subsequently loaded with the H<sub>2</sub>S donor ADT-OH and coated with tumor cell membranes for homotypic targeting. Upon exposure to an alternating magnetic field (AMF), the Fe<sub>3</sub>O<sub>4</sub>@MIL-100 core enables localized hyperthermia, while acidic tumor microenvironment triggers ADT-OH release for sustained H<sub>2</sub>S generation. The released H<sub>2</sub>S enhances tumor cell sensitivity to hyperthermia by inhibiting NF-κB activation and downregulating HSP expression. Suprisingly, H<sub>2</sub>S can also augment the MN induced ferroptosis. In vitro and in vivo studies have demonstrated that CmMN@ADT effectively induces tumor ablation and elicits potent anti-tumor immune responses, ultimately achieving the inhibition of the growth of both primary and metastatic tumors. Collectively, this study presents a novel H<sub>2</sub>S driven magnetic MOF nanoplatform that achieves dual mode synergy between H<sub>2</sub>S Augmented MHT and ferroptosis, providing a mechanistically guided strategy to overcome tumor thermotolerance and achieve durable tumor suppression.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102892"},"PeriodicalIF":10.2,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170414","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}
Pub Date : 2026-02-02DOI: 10.1016/j.mtbio.2026.102889
Yun Xue , Aoao Wang , Fei Liu , Zhengkai Han , Aichen Zhu , Yang Liu , Jingshuang Zhang , Shuai Lu , Qiang Dai , You Zhou , Xiaohua Hu , Rui Shi
Large-volume skin defects, such as diabetic ulcers and burns, pose a significant clinical challenge due to impaired healing capacity and a lack of effective treatment options. Although mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are well-established promoters of angiogenesis in wound healing, their multi-mechanistic regulatory networks and functionalities when integrated with biomaterials are not fully elucidated. In this study, we developed a core-shell polycaprolactone/gelatin nanofiber scaffold incorporating bone marrow MSC-EVs (PCL-EVs). The incorporation of PCL-EVs enhanced the scaffold's hydrophilicity, which in turn facilitated cell adhesion and proliferation. Functionally, the PCL-EVs scaffold suppressed pro-inflammatory cytokine release, enhanced endothelial tubule formation, promoted fibroblast lipid catabolism, and increased mitochondrial abundance. Mechanistically, PCL-EVs mediated angiogenesis through upregulation of HIF-1α-VEGF signaling and cGMP-PKG cascades. Furthermore, PCL-EVs modulated inflammatory responses by inhibiting the PANoptosis pathway, leading to a reduction in pro-inflammatory cytokines. In fibroblasts, PCL-EVs induced metabolic reprogramming characterized by increased lipolysis and mitochondrial biogenesis, thereby boosting ATP and metabolite production to support tissue repair. In a rat large full-thickness excisional wound splinting model, the PCL-EV nanofiber scaffold demonstrated significant potential for remodeling skin defects. This study not only developed a biomimetic core-shell scaffold as a sustained-release platform for MSC-EVs but also elucidated the mechanisms through which it promotes full-thickness wound healing, demonstrating its multi-faceted role in enhancing angiogenesis, immunomodulation, and metabolic reprogramming.
{"title":"Extracellular vesicle-integrated core-shell nanofibers synergize multi-target healing mechanisms for accelerated repair of large-volume skin defects","authors":"Yun Xue , Aoao Wang , Fei Liu , Zhengkai Han , Aichen Zhu , Yang Liu , Jingshuang Zhang , Shuai Lu , Qiang Dai , You Zhou , Xiaohua Hu , Rui Shi","doi":"10.1016/j.mtbio.2026.102889","DOIUrl":"10.1016/j.mtbio.2026.102889","url":null,"abstract":"<div><div>Large-volume skin defects, such as diabetic ulcers and burns, pose a significant clinical challenge due to impaired healing capacity and a lack of effective treatment options. Although mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are well-established promoters of angiogenesis in wound healing, their multi-mechanistic regulatory networks and functionalities when integrated with biomaterials are not fully elucidated. In this study, we developed a core-shell polycaprolactone/gelatin nanofiber scaffold incorporating bone marrow MSC-EVs (PCL-EVs). The incorporation of PCL-EVs enhanced the scaffold's hydrophilicity, which in turn facilitated cell adhesion and proliferation. Functionally, the PCL-EVs scaffold suppressed pro-inflammatory cytokine release, enhanced endothelial tubule formation, promoted fibroblast lipid catabolism, and increased mitochondrial abundance. Mechanistically, PCL-EVs mediated angiogenesis through upregulation of HIF-1α-VEGF signaling and cGMP-PKG cascades. Furthermore, PCL-EVs modulated inflammatory responses by inhibiting the PANoptosis pathway, leading to a reduction in pro-inflammatory cytokines. In fibroblasts, PCL-EVs induced metabolic reprogramming characterized by increased lipolysis and mitochondrial biogenesis, thereby boosting ATP and metabolite production to support tissue repair. In a rat large full-thickness excisional wound splinting model, the PCL-EV nanofiber scaffold demonstrated significant potential for remodeling skin defects. This study not only developed a biomimetic core-shell scaffold as a sustained-release platform for MSC-EVs but also elucidated the mechanisms through which it promotes full-thickness wound healing, demonstrating its multi-faceted role in enhancing angiogenesis, immunomodulation, and metabolic reprogramming.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102889"},"PeriodicalIF":10.2,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170328","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}
Pub Date : 2026-02-01DOI: 10.1016/j.mtbio.2026.102885
Qiufang Gong , Lutong Wen , Qiuchen Wang , Yiheng Xia , Mei Zhang , Bo Sun , Tianqing Zhang , Hongyu Zhang , Dongliang Yang , Xuejiao Song , Jingbo Dong , Chao Liang
Diabetic abscesses represent a severe and challenging complication of chronic wounds, characterized by impaired healing due to hyperglycemia-induced oxidative stress, persistent inflammation, and susceptibility to infection. Despite advances in wound care, effective therapeutic strategies that simultaneously address these multifactorial pathologies remain lacking. Herein, we developed cerium molybdate nanoparticles (CeMo) through a green one-pot method as multifunctional therapeutic platforms for diabetic abscess treatment. CeMo exhibited dual enzyme-mimetic activities, serving as superoxide dismutase and catalase to catalytically eliminate reactive oxygen species (ROS) with over 90% scavenging efficiency at 100 μg/mL. Furthermore, they demonstrated exceptional photothermal conversion efficiency with a 30% conversion efficiency under 808 nm laser irradiation, enabling effective disruption of methicillin-resistant Staphylococcus aureus (MRSA). In vitro studies validated their ability to alleviate oxidative stress, facilitate macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype. In a diabetic murine abscess model, CeMo synergistically combined stable photothermal antibacterial activity, broad-spectrum ROS scavenging capability, and efficient immunomodulation to accelerate wound closure, achieving 90% healing within 12 days versus 35% in controls, while promoting collagen deposition and tissue remodeling. This work presents a promising strategy for managing infected diabetic wounds through multimodal microenvironment reprogramming.
{"title":"Rewiring diabetic abscess microenvironment for healing via CeMo-mediated photothermal antibacterial, ROS scavenging and immunomodulatory","authors":"Qiufang Gong , Lutong Wen , Qiuchen Wang , Yiheng Xia , Mei Zhang , Bo Sun , Tianqing Zhang , Hongyu Zhang , Dongliang Yang , Xuejiao Song , Jingbo Dong , Chao Liang","doi":"10.1016/j.mtbio.2026.102885","DOIUrl":"10.1016/j.mtbio.2026.102885","url":null,"abstract":"<div><div>Diabetic abscesses represent a severe and challenging complication of chronic wounds, characterized by impaired healing due to hyperglycemia-induced oxidative stress, persistent inflammation, and susceptibility to infection. Despite advances in wound care, effective therapeutic strategies that simultaneously address these multifactorial pathologies remain lacking. Herein, we developed cerium molybdate nanoparticles (CeMo) through a green one-pot method as multifunctional therapeutic platforms for diabetic abscess treatment. CeMo exhibited dual enzyme-mimetic activities, serving as superoxide dismutase and catalase to catalytically eliminate reactive oxygen species (ROS) with over 90% scavenging efficiency at 100 μg/mL. Furthermore, they demonstrated exceptional photothermal conversion efficiency with a 30% conversion efficiency under 808 nm laser irradiation, enabling effective disruption of methicillin-resistant <em>Staphylococcus aureus</em> (MRSA). In vitro studies validated their ability to alleviate oxidative stress, facilitate macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype. In a diabetic murine abscess model, CeMo synergistically combined stable photothermal antibacterial activity, broad-spectrum ROS scavenging capability, and efficient immunomodulation to accelerate wound closure, achieving 90% healing within 12 days versus 35% in controls, while promoting collagen deposition and tissue remodeling. This work presents a promising strategy for managing infected diabetic wounds through multimodal microenvironment reprogramming.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102885"},"PeriodicalIF":10.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169946","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}
Bacterial combination therapy offers immense promise for treating aggressive "cold" solid tumors, such as triple-negative breast cancer (TNBC). However, the clinical translatability of traditional genetic engineering is often hampered by operational complexity and genetic instability. Here, we developed A-SPB—a non-genetically engineered, multi-functional living bioreactor based on Shewanella oneidensis MR-1 (SO), surface-modified with Prussian blue (PB) nanoparticles and attenuated via deoxycholic acid (DA) treatment. This platform serves as an in situ metabolic factory that "hijacks" the sulfur-metabolism within the hypoxic tumor microenvironment. By actively depleting cysteine, A-SPB not only starves the glutathione (GSH) synthesis pathway but also generates hydrogen sulfide (H2S) to inhibit the transsulfuration bypass, leading to a dual-pronged collapse of the GSH/GPX4 antioxidant axis and triggering robust tumor ferroptosis. This metabolic sensitization is further amplified by the PB-mediated photothermal therapy (PTT), which generates localized hyperthermia and excessive reactive oxygen species (ROS). Notably, the PTT serves as a dual-functional "bio-switch": it promotes acute tumor ablation while simultaneously triggering bacterial self-lysis to ensure biosafety. This programmed lysis releases a synergistic cocktail of bacterial PAMPs and tumor-derived DAMPs, which effectively remodels the immunosuppressive TME and initiates a potent systemic antitumor immune response. By integrating metabolic reprogramming, sensitized ferroptosis, and on-demand immune activation through simple surface engineering, this study provides a highly translatable and safe paradigm for the next generation of living bacterial therapeutics.
{"title":"Living bacterial reactor potently activates tumor immunogenic ferroptosis via cysteine depletion and photothermal therapy","authors":"Mengen Guo , Wenjie Xu , Yanjin Peng , Yucheng Tang , Xinyan Hao , Tiantian Tang , Xinying Liu , Hai Huang , Ruyue Han , Junyong Wu , Daxiong Xiang","doi":"10.1016/j.mtbio.2026.102843","DOIUrl":"10.1016/j.mtbio.2026.102843","url":null,"abstract":"<div><div>Bacterial combination therapy offers immense promise for treating aggressive \"cold\" solid tumors, such as triple-negative breast cancer (TNBC). However, the clinical translatability of traditional genetic engineering is often hampered by operational complexity and genetic instability. Here, we developed A-SPB—a non-genetically engineered, multi-functional living bioreactor based on <em>Shewanella oneidensis</em> MR-1 (SO), surface-modified with Prussian blue (PB) nanoparticles and attenuated via deoxycholic acid (DA) treatment. This platform serves as an <em>in situ</em> metabolic factory that \"hijacks\" the sulfur-metabolism within the hypoxic tumor microenvironment. By actively depleting cysteine, A-SPB not only starves the glutathione (GSH) synthesis pathway but also generates hydrogen sulfide (H<sub>2</sub>S) to inhibit the transsulfuration bypass, leading to a dual-pronged collapse of the GSH/GPX4 antioxidant axis and triggering robust tumor ferroptosis. This metabolic sensitization is further amplified by the PB-mediated photothermal therapy (PTT), which generates localized hyperthermia and excessive reactive oxygen species (ROS). Notably, the PTT serves as a dual-functional \"bio-switch\": it promotes acute tumor ablation while simultaneously triggering bacterial self-lysis to ensure biosafety. This programmed lysis releases a synergistic cocktail of bacterial PAMPs and tumor-derived DAMPs, which effectively remodels the immunosuppressive TME and initiates a potent systemic antitumor immune response. By integrating metabolic reprogramming, sensitized ferroptosis, and on-demand immune activation through simple surface engineering, this study provides a highly translatable and safe paradigm for the next generation of living bacterial therapeutics.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102843"},"PeriodicalIF":10.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170387","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}
Pub Date : 2026-02-01DOI: 10.1016/j.mtbio.2026.102863
Jing Sun, Xi Wang, Xiaoxue Wang, Wenhui Yu, Yang Yu, Shaohua Ge, Zheqin Dong
Guided bone regeneration (GBR) membranes are widely used for the treatment of bone defects. Natural hydrogels are promising candidates for GBR membranes owing to their excellent bioactivity and controllable degradability, but their clinical translation is restricted by inherent mechanical weakness. Inspired by tendon-strengthening mechanisms in athletes, we propose a tannic acid (TA)-assisted wet-stretching (TAWS) strategy to transform gelatin methacryloyl (GelMA) hydrogels into mechanically robust GBR membranes. During stretching, GelMA chains are directionally aligned while TA establishes multivalent hydrogen bonds between adjacent fibers, synergistically reinforcing the network. The resulting TA-trained (GHT) membranes achieved a 22.16-fold increase in Young's modulus and a 12.31-fold enhancement in toughness. In parallel, TAWS markedly slowed degradation kinetics and enhanced physiological stability, enabling GHT membranes to retain ∼80 % of their initial mass after 28 days in SBF. Beyond reinforcement, TA imparted potent ROS-scavenging and immunomodulatory activity. In vitro, GHT membranes enhanced stem cell survival, proliferation, and osteogenic differentiation under oxidative stress. In a mandibular defect model under elevated oxidative and inflammatory challenge, GHT reduced ROS levels (DHE fluorescence) to 53.76 % of the untreated ROS-upregulated group and increased bone volume fraction (BV/TV) by approximately 2.68-fold at 4 weeks and 2.21-fold at 8 weeks, outperforming the Bio-Gide® membrane. Collectively, TAWS provides a scalable platform to engineer multifunctional hydrogel membranes that integrate mechanics, stability, and regenerative performance for advanced GBR.
{"title":"Tannic acid-assisted mechanical training transforms natural hydrogels into robust and bioactive membranes for guided bone regeneration","authors":"Jing Sun, Xi Wang, Xiaoxue Wang, Wenhui Yu, Yang Yu, Shaohua Ge, Zheqin Dong","doi":"10.1016/j.mtbio.2026.102863","DOIUrl":"10.1016/j.mtbio.2026.102863","url":null,"abstract":"<div><div>Guided bone regeneration (GBR) membranes are widely used for the treatment of bone defects. Natural hydrogels are promising candidates for GBR membranes owing to their excellent bioactivity and controllable degradability, but their clinical translation is restricted by inherent mechanical weakness. Inspired by tendon-strengthening mechanisms in athletes, we propose a tannic acid (TA)-assisted wet-stretching (TAWS) strategy to transform gelatin methacryloyl (GelMA) hydrogels into mechanically robust GBR membranes. During stretching, GelMA chains are directionally aligned while TA establishes multivalent hydrogen bonds between adjacent fibers, synergistically reinforcing the network. The resulting TA-trained (GHT) membranes achieved a 22.16-fold increase in Young's modulus and a 12.31-fold enhancement in toughness. In parallel, TAWS markedly slowed degradation kinetics and enhanced physiological stability, enabling GHT membranes to retain ∼80 % of their initial mass after 28 days in SBF. Beyond reinforcement, TA imparted potent ROS-scavenging and immunomodulatory activity. In vitro, GHT membranes enhanced stem cell survival, proliferation, and osteogenic differentiation under oxidative stress. In a mandibular defect model under elevated oxidative and inflammatory challenge, GHT reduced ROS levels (DHE fluorescence) to 53.76 % of the untreated ROS-upregulated group and increased bone volume fraction (BV/TV) by approximately 2.68-fold at 4 weeks and 2.21-fold at 8 weeks, outperforming the Bio-Gide® membrane. Collectively, TAWS provides a scalable platform to engineer multifunctional hydrogel membranes that integrate mechanics, stability, and regenerative performance for advanced GBR.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102863"},"PeriodicalIF":10.2,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170389","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}
Pub Date : 2026-01-31DOI: 10.1016/j.mtbio.2026.102862
Tingting Liu , Wenyan She , Ruili Du , Yali Bao , Zhibin Guo , Qichao Gao , Hanping Li , Pengfei Suo , Yi Liu , Yujiao Liu
It is important yet challenging to enhance immunotherapy responses using biosafe agents due to the immunosuppressive tumor microenvironment. To address this challenge, BD3PP was constructed by encapsulating black phosphorus quantum dots (BPQDs), a synthesized thioredoxin reductase inhibitor 3c, and Dir (the fluorescent dye) into PLGA nanoparticles, followed by conjugation with a PDL1 antagonist for synergistic multimodal therapy and imaging. The mechanism and efficiency of BD3PP were investigated through density functional theory (DFT) calculations, molecular docking, and in vitro and in vivo experiments. The PDL1 antagonist served as a targeting moiety that binds PDL1 on the tumor cell surface, enabling the controlled intracellular release of the three therapeutic agents. Self-passivated bilayer BPQDs converted optical energy into heat for photothermal therapy and generated singlet oxygen (1O2) from O2 for type II photodynamic therapy, showing far superior to non-passivated bilayer BPQDs or bulk BP. Meanwhile, 3c selectively inhibited thioredoxin reductase, leading to the production of · and H2O2. These effects synergistically induced immunogenic cell death (ICD), promoted macrophage polarization toward the M1 phenotype, and remodeled the tumor microenvironment to facilitate tumor clearance. The near-infrared fluorescent dye Dir enabled real-time imaging both in vitro and in vivo. DFT calculation revealed that BPQDs were ultimately degraded into biocompatible phosphoric acid. Along with the other biocompatible components in BD3PP, biosafety was guaranteed. This research introduces an efficient and biosafe nanoplatform based on self-passivated bilayer BPQDs, which exhibits prolonged blood circulation and enhanced multimodal real-time photothermal and near-infrared imaging. Importantly, this nanoplatform enables integrated photothermal, photodynamic, and targeted therapies, demonstrating promising potential for anti-tumor preclinical and clinical applications.
{"title":"Self-passivated bilayer black phosphorus QDs based multifunctional nanoparticles for tumor immune reprogramming","authors":"Tingting Liu , Wenyan She , Ruili Du , Yali Bao , Zhibin Guo , Qichao Gao , Hanping Li , Pengfei Suo , Yi Liu , Yujiao Liu","doi":"10.1016/j.mtbio.2026.102862","DOIUrl":"10.1016/j.mtbio.2026.102862","url":null,"abstract":"<div><div>It is important yet challenging to enhance immunotherapy responses using biosafe agents due to the immunosuppressive tumor microenvironment. To address this challenge, BD3PP was constructed by encapsulating black phosphorus quantum dots (BPQDs), a synthesized thioredoxin reductase inhibitor 3c, and Dir (the fluorescent dye) into PLGA nanoparticles, followed by conjugation with a PDL1 antagonist for synergistic multimodal therapy and imaging. The mechanism and efficiency of BD3PP were investigated through density functional theory (DFT) calculations, molecular docking, and <em>in vitro</em> and <em>in vivo</em> experiments. The PDL1 antagonist served as a targeting moiety that binds PDL1 on the tumor cell surface, enabling the controlled intracellular release of the three therapeutic agents. Self-passivated bilayer BPQDs converted optical energy into heat for photothermal therapy and generated singlet oxygen (<sup>1</sup>O<sub>2</sub>) from O<sub>2</sub> for type II photodynamic therapy, showing far superior to non-passivated bilayer BPQDs or bulk BP. Meanwhile, <strong>3c</strong> selectively inhibited thioredoxin reductase, leading to the production of <strong>·</strong> <span><math><mrow><msubsup><mi>O</mi><mn>2</mn><mo>‐</mo></msubsup></mrow></math></span> and H<sub>2</sub>O<sub>2</sub>. These effects synergistically induced immunogenic cell death (ICD), promoted macrophage polarization toward the M1 phenotype, and remodeled the tumor microenvironment to facilitate tumor clearance. The near-infrared fluorescent dye Dir enabled real-time imaging both <em>in vitro</em> and <em>in vivo</em>. DFT calculation revealed that BPQDs were ultimately degraded into biocompatible phosphoric acid. Along with the other biocompatible components in BD3PP, biosafety was guaranteed. This research introduces an efficient and biosafe nanoplatform based on self-passivated bilayer BPQDs, which exhibits prolonged blood circulation and enhanced multimodal real-time photothermal and near-infrared imaging. Importantly, this nanoplatform enables integrated photothermal, photodynamic, and targeted therapies, demonstrating promising potential for anti-tumor preclinical and clinical applications.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102862"},"PeriodicalIF":10.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170386","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}
Pub Date : 2026-01-31DOI: 10.1016/j.mtbio.2026.102867
Zhaoting Wang , Xiaoxiong Xiao , Tianlu Zhang , Xiao Li , Mengmeng Ji , Yongqi Qian , Xue Bai , Xin Li , Jing Lu , Jinlu Tang , Kangdong Liu , Zhaohui Li , Baoyin Yuan
Esophageal squamous cell carcinoma (ESCC), a prevalent subtype of esophageal cancer, poses a significant global health challenge. The current diagnostic and therapeutic approaches for ESCC are inadequate, highlighting the urgent need for the development of novel recognition molecules and the identification of new therapeutic targets to facilitate early diagnosis and targeted therapy. In this work, several aptamers with high affinity to target KYSE30 cells are screened through Cell-based Systematic Evolution of Ligands by EXponential enrichment (Cell-SELEX). These aptamers show distinct binding to multiple cancer cells including ESCC, gastric cancer and liver cancer cells. Meanwhile, a truncated aptamer Z4-6 that retains comparable binding affinity is achieved via sequence optimization. With Z2 and Z4-6 aptamers as the recognition elements, Cy5-labeled fluorescent aptamer probes have demonstrated the ability to specifically recognize ESCC tissues while sparing adjacent non-cancerous tissues, suggesting their potential utility as detection probes in the clinical diagnosis of ESCC. Furthermore, myosin 1B has been identified as the molecular target of the aptamer Z4-6 through pull-down and RNA interference assays, underscoring its promise as a tumor biomarker and therapeutic target. The Z4-6 aptamer has been employed to construct Z4-6-Dox conjugates via noncovalent loading with doxorubicin (Dox) for the targeted therapy of ESCC. In vitro cytotoxicity assays have revealed that Z4-6-Dox selectively induces cytotoxicity in KYSE30 cells. Notably, the Z4-6 aptamer demonstrates in vivo tumor-targeting capabilities, and Z4-6-Dox effectively inhibits tumor cell growth with reduced cardiotoxicity. This study contributes valuable molecular recognition tools and identifies a potential target for the precise diagnosis and targeted therapy of ESCC.
{"title":"Identification of a myosin 1B-binding aptamer for fluorescence imaging and targeted therapy of esophageal squamous cell carcinoma","authors":"Zhaoting Wang , Xiaoxiong Xiao , Tianlu Zhang , Xiao Li , Mengmeng Ji , Yongqi Qian , Xue Bai , Xin Li , Jing Lu , Jinlu Tang , Kangdong Liu , Zhaohui Li , Baoyin Yuan","doi":"10.1016/j.mtbio.2026.102867","DOIUrl":"10.1016/j.mtbio.2026.102867","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC), a prevalent subtype of esophageal cancer, poses a significant global health challenge. The current diagnostic and therapeutic approaches for ESCC are inadequate, highlighting the urgent need for the development of novel recognition molecules and the identification of new therapeutic targets to facilitate early diagnosis and targeted therapy. In this work, several aptamers with high affinity to target KYSE30 cells are screened through Cell-based Systematic Evolution of Ligands by EXponential enrichment (Cell-SELEX). These aptamers show distinct binding to multiple cancer cells including ESCC, gastric cancer and liver cancer cells. Meanwhile, a truncated aptamer Z4-6 that retains comparable binding affinity is achieved via sequence optimization. With Z2 and Z4-6 aptamers as the recognition elements, Cy5-labeled fluorescent aptamer probes have demonstrated the ability to specifically recognize ESCC tissues while sparing adjacent non-cancerous tissues, suggesting their potential utility as detection probes in the clinical diagnosis of ESCC. Furthermore, myosin 1B has been identified as the molecular target of the aptamer Z4-6 through pull-down and RNA interference assays, underscoring its promise as a tumor biomarker and therapeutic target. The Z4-6 aptamer has been employed to construct Z4-6-Dox conjugates via noncovalent loading with doxorubicin (Dox) for the targeted therapy of ESCC. In vitro cytotoxicity assays have revealed that Z4-6-Dox selectively induces cytotoxicity in KYSE30 cells. Notably, the Z4-6 aptamer demonstrates in vivo tumor-targeting capabilities, and Z4-6-Dox effectively inhibits tumor cell growth with reduced cardiotoxicity. This study contributes valuable molecular recognition tools and identifies a potential target for the precise diagnosis and targeted therapy of ESCC.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102867"},"PeriodicalIF":10.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170456","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}
Pub Date : 2026-01-31DOI: 10.1016/j.mtbio.2026.102874
Weiqing Fang , Jing Zhao , Li Li , Yu Wang , Zhi Ping Xu , Lingxiao Zhang
β-amyloid (Aβ) inhibition significantly attenuates the early-stage Alzheimer's disease (AD) progression, but the improvement in cognitive function remains limited by neuroinflammation. Here, we developed a bioinspired neuroenhancer that concurrently targets both Aβ aggregation and neuroinflammation. Rutin and small interfering RNA targeting beta-site amyloid precursor protein cleaving enzyme 1 (siBACE1) were co-loaded into the calcium phosphate core, which was further coated with lipid bilayers and Angiopep-2/rabies virus glycoprotein 29 peptides to form the multifunctional neuroenhancer (RB@LCP-AR). RB@LCP-AR not only releases siBACE1 to silence BACE1 expression and block Aβ production from the cleavage of amyloid precursor protein, but also releases Rutin to suppress the Aβ aggregation. Moreover, the released Rutin of RB@LCP-AR directly alleviates Aβ-induced mitochondria dysfunction and intracellular ROS production in neuronal cells. Notably, the targeting of RB@LCP-AR to neurons and the inhibition of Aβ reduce the microgliosis and astrogliosis, further alleviating neuroinflammation and synapse loss. Consequently, AD mice receiving RB@LCP-AR treatment efficiently recovered their memory and cognition. Our study thus provides a coordinated targeting of Aβ and neuroinflammation inhibition, holding considerable potential to promote the recovery of memory and cognition in AD.
{"title":"An anti-inflammatory neuroenhancer mitigates amyloid-β pathology to improve Alzheimer's disease therapy","authors":"Weiqing Fang , Jing Zhao , Li Li , Yu Wang , Zhi Ping Xu , Lingxiao Zhang","doi":"10.1016/j.mtbio.2026.102874","DOIUrl":"10.1016/j.mtbio.2026.102874","url":null,"abstract":"<div><div>β-amyloid (Aβ) inhibition significantly attenuates the early-stage Alzheimer's disease (AD) progression, but the improvement in cognitive function remains limited by neuroinflammation. Here, we developed a bioinspired neuroenhancer that concurrently targets both Aβ aggregation and neuroinflammation. Rutin and small interfering RNA targeting beta-site amyloid precursor protein cleaving enzyme 1 (siBACE1) were co-loaded into the calcium phosphate core, which was further coated with lipid bilayers and Angiopep-2/rabies virus glycoprotein 29 peptides to form the multifunctional neuroenhancer (RB@LCP-AR). RB@LCP-AR not only releases siBACE1 to silence BACE1 expression and block Aβ production from the cleavage of amyloid precursor protein, but also releases Rutin to suppress the Aβ aggregation. Moreover, the released Rutin of RB@LCP-AR directly alleviates Aβ-induced mitochondria dysfunction and intracellular ROS production in neuronal cells. Notably, the targeting of RB@LCP-AR to neurons and the inhibition of Aβ reduce the microgliosis and astrogliosis, further alleviating neuroinflammation and synapse loss. Consequently, AD mice receiving RB@LCP-AR treatment efficiently recovered their memory and cognition. Our study thus provides a coordinated targeting of Aβ and neuroinflammation inhibition, holding considerable potential to promote the recovery of memory and cognition in AD.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102874"},"PeriodicalIF":10.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170510","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}
Pub Date : 2026-01-31DOI: 10.1016/j.mtbio.2026.102883
Fenghua Zhao , Xue Zhang , Theo Borghuis , Linda A. Brouwer , Janette K. Burgess , Prashant K. Sharma , Martin C. Harmsen
Cells continuously sense and adapt to the mechanical properties of their surrounding extracellular matrix (ECM), yet how human umbilical cord–derived mesenchymal stromal cells (UC-MSCs) mechanotransduce stiffness cues in 3D ECM remains incompletely understood. This knowledge gap limits the rational design of MSC-based regenerative therapies and mechanically instructive biomaterials. Here, using ruthenium-catalyzed photocrosslinked skin-derived ECM hydrogels spanning a physiological to fibrotic stiffness range, we demonstrate that UC-MSCs exhibit distinct, stiffness-dependent remodeling strategies. Soft matrices (1.2 kPa) induced cell-mediated hydrogel contraction, medium stiffness (3.4 kPa, comparable to native skin) supported elongated cell morphology with minimal remodeling, whereas stiff matrices (17.7 kPa) kept seeded UC-MSCs rounded and induced pericellular void formation consistent with localized ECM remodeling. By decoupling geometric contraction from intrinsic ECM turnover using volume-normalized mechanical analyses, we identify the Piezo1 as a key regulator of stiffness-dependent adaptation. Piezo1 expression increased with stiffness, and its inhibition attenuated contraction in soft matrices and prevented stiffness reduction in stiff matrices, indicating that Piezo1 enables MSCs to mechanically adapt across 3D microenvironments. Analysis of matrix metalloproteinase expression revealed stiffness-dependent regulation of MMP2 and MMP14; however, their expression was only marginally affected by Piezo1 inhibition, suggesting that Piezo1 influences ECM remodeling through mechanisms beyond direct regulation of MMP expression. Together, these findings establish a mechanistic framework in which UC-MSCs adapt to 3D ECM stiffness through Piezo1-dependent mechanosensing. This work provides conceptual and practical guidance for the design of mechanically programmable biomaterials, the optimization of MSC-based regenerative strategies, and therapeutic approaches aimed at modulating pathological tissue mechanics such as fibrosis.
{"title":"Piezo1 regulates remodeling of skin-derived extracellular matrix by embedded umbilical cord mesenchymal stem cells in a stiffness-dependent fashion","authors":"Fenghua Zhao , Xue Zhang , Theo Borghuis , Linda A. Brouwer , Janette K. Burgess , Prashant K. Sharma , Martin C. Harmsen","doi":"10.1016/j.mtbio.2026.102883","DOIUrl":"10.1016/j.mtbio.2026.102883","url":null,"abstract":"<div><div>Cells continuously sense and adapt to the mechanical properties of their surrounding extracellular matrix (ECM), yet how human umbilical cord–derived mesenchymal stromal cells (UC-MSCs) mechanotransduce stiffness cues in 3D ECM remains incompletely understood. This knowledge gap limits the rational design of MSC-based regenerative therapies and mechanically instructive biomaterials. Here, using ruthenium-catalyzed photocrosslinked skin-derived ECM hydrogels spanning a physiological to fibrotic stiffness range, we demonstrate that UC-MSCs exhibit distinct, stiffness-dependent remodeling strategies. Soft matrices (1.2 kPa) induced cell-mediated hydrogel contraction, medium stiffness (3.4 kPa, comparable to native skin) supported elongated cell morphology with minimal remodeling, whereas stiff matrices (17.7 kPa) kept seeded UC-MSCs rounded and induced pericellular void formation consistent with localized ECM remodeling. By decoupling geometric contraction from intrinsic ECM turnover using volume-normalized mechanical analyses, we identify the Piezo1 as a key regulator of stiffness-dependent adaptation. Piezo1 expression increased with stiffness, and its inhibition attenuated contraction in soft matrices and prevented stiffness reduction in stiff matrices, indicating that Piezo1 enables MSCs to mechanically adapt across 3D microenvironments. Analysis of matrix metalloproteinase expression revealed stiffness-dependent regulation of MMP2 and MMP14; however, their expression was only marginally affected by Piezo1 inhibition, suggesting that Piezo1 influences ECM remodeling through mechanisms beyond direct regulation of MMP expression. Together, these findings establish a mechanistic framework in which UC-MSCs adapt to 3D ECM stiffness through Piezo1-dependent mechanosensing. This work provides conceptual and practical guidance for the design of mechanically programmable biomaterials, the optimization of MSC-based regenerative strategies, and therapeutic approaches aimed at modulating pathological tissue mechanics such as fibrosis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102883"},"PeriodicalIF":10.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170513","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}
Pub Date : 2026-01-31DOI: 10.1016/j.mtbio.2026.102881
Ji-Yeon Park , Hye-Seon Jeong , Seong-Ryeong Lim , Won-Kyo Jung , Jae-Young Je , Chang-Hyung Choi , Sei-Jung Lee
Inflammatory bowel disease (IBD) encompasses chronic or relapsing inflammation within different regions of the gastrointestinal tract. Pentoxifylline (PTX), a methylxanthine derivative primarily used to improve blood flow in peripheral vascular diseases, has demonstrated anti-inflammatory and immunomodulatory properties, suggesting its potential in attenuating IBD-associated inflammation. However, its clinical application in IBD remains limited, partly due to its short half-life and poor targeting to inflamed intestinal tissues, necessitating strategies to enhance its bioavailability and tissue-specific delivery. To address this limitation, we developed a targeted drug delivery system utilizing a microfluidic approach to fabricate pH-responsive core–shell hydrogel microcapsules encapsulating PTX, referred to as PTX-loaded hydrogel microcapsules (PHM), for enhanced delivery to inflamed colonic tissue. These microcapsules were generated via photopolymerization of triple emulsion droplets, resulting in a structure composed of a poly (acrylic acid)-poly (ethylene glycol) diacrylate (PAA–PEGDA) shell and a PEGDA core, separated by a thin oil layer. The oil layer serves as a protective barrier against the acidic gastric environment, while the pH-responsive swelling of the PAA–PEGDA shell at basic pH (7.5) compresses and destabilizes the oil layer, thereby enabling controlled PTX release specifically in the colonic environment. In vivo studies using dextran sulfate sodium (DSS)-induced IBD in ICR mice demonstrate that PHM significantly mitigates disease severity, as evidenced by an approximately 38.5% reduction in disease activity index scores, restoration of mucosal architecture, and decreased infiltration of colonic macrophages. In parallel, PHM treatment markedly suppresses colonic inflammatory responses, lowering IL-1β by 40%, IL-6 by 66.2%, and TNF-α by 36.2% compared to DSS-treated mice, along with a broader reduction of pro-inflammatory mediators, highlighting its anti-inflammatory potential. Notably, PHM also contributes to the rebalancing of dysbiotic gut microbiota, including the restoration of beneficial genera such as Bacteroides acidifaciens and PAC001120_s, thereby promoting microbial homeostasis. Collectively, these findings underscore PHM as a promising PTX-based therapeutic strategy for effective IBD intervention.
{"title":"Triple-emulsion microfluidic Core–Shell hydrogel microcapsules for oral pentoxifylline Delivery: Ameliorating colitis and rebalancing gut microbiome","authors":"Ji-Yeon Park , Hye-Seon Jeong , Seong-Ryeong Lim , Won-Kyo Jung , Jae-Young Je , Chang-Hyung Choi , Sei-Jung Lee","doi":"10.1016/j.mtbio.2026.102881","DOIUrl":"10.1016/j.mtbio.2026.102881","url":null,"abstract":"<div><div><strong>Inflammatory bowel disease (IBD) encompasses chronic or relapsing inflammation within different regions of the gastrointestinal tract. Pentoxifylline (PTX)</strong>, a methylxanthine derivative primarily used to improve blood flow in peripheral vascular diseases, has demonstrated anti-inflammatory and immunomodulatory properties, suggesting its potential in attenuating IBD-associated inflammation. However, its clinical application in IBD remains limited, partly due to its short half-life and poor targeting to inflamed intestinal tissues, necessitating strategies to enhance its bioavailability and tissue-specific delivery. To address this limitation, we developed a targeted drug delivery system utilizing a microfluidic approach to fabricate pH-responsive core–shell hydrogel microcapsules encapsulating PTX, referred to as PTX-loaded hydrogel microcapsules (PHM), for enhanced delivery to inflamed colonic tissue. These microcapsules were generated via photopolymerization of triple emulsion droplets, resulting in a structure composed of a poly (acrylic acid)-poly (ethylene glycol) diacrylate (PAA–PEGDA) shell and a PEGDA core, separated by a thin oil layer. The oil layer serves as a protective barrier against the acidic gastric environment, while the pH-responsive swelling of the PAA–PEGDA shell at basic pH (7.5) compresses and destabilizes the oil layer, thereby enabling controlled PTX release specifically in the colonic environment. <em>In vivo</em> studies using dextran sulfate sodium (DSS)-induced IBD in ICR mice demonstrate that PHM significantly mitigates disease severity, as evidenced by an approximately 38.5% reduction in disease activity index scores, restoration of mucosal architecture, and decreased infiltration of colonic macrophages. In parallel, PHM treatment markedly suppresses colonic inflammatory responses, lowering IL-1β by 40%, IL-6 by 66.2%, and TNF-α by 36.2% compared to DSS-treated mice, along with a broader reduction of pro-inflammatory mediators, highlighting its anti-inflammatory potential. Notably, PHM also contributes to the rebalancing of dysbiotic gut microbiota, including the restoration of beneficial genera such as <em>Bacteroides acidifaciens</em> and <em>PAC001120_s</em>, thereby promoting microbial homeostasis. Collectively, these findings underscore PHM as a promising PTX-based therapeutic strategy for effective IBD intervention.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102881"},"PeriodicalIF":10.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169945","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}
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