Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.mtbio.2026.102823
Liwen Chen , Chao Shang , Yang Hong , Hui Zhang
Glioblastoma (GBM) is a highly aggressive brain tumor that offers few treatment options. Current therapeutic approaches face challenges such as poor drug delivery precision, low accumulation at tumor sites, and significant toxicity to normal tissues. To address these issues, this study designed a targeted drug delivery platform by modifying liposomes with the tumor-homing peptide A2b11, which specifically binds to the GBM-associated antigen IL13RA2. A2b11-liposomes loaded with sodium fluorescein (FLA) and A2b11-liposomes loaded with temozolomide (TLA) were evaluated for their anti-GBM effects. In vitro, studies demonstrated that A2b11-modified liposomes significantly enhanced accumulation in GBM cells and enhanced their anti-GBM efficacy compared to unmodified liposomes. In vivo, experiments using xenograft tumor mouse models showed that the targeted drug delivery platform exhibited good biocompatibility and in vivo safety. Compared to other organs, FLA demonstrated significantly higher accumulation at tumor sites, showcasing its potential for targeted therapy and enabling assessment of its effects on inducing apoptosis and inhibiting angiogenesis. Additionally, TLA induced GBM cell apoptosis and reduced tumor angiogenesis, highlighting its significant potential in inhibiting GBM tumor growth. The A2b11 peptide-modified liposomal system developed in this study represents a promising platform for GBM-targeted therapy. Further research and development of this platform could lay the groundwork for its future clinical application.
{"title":"Development and evaluation of IL13RA2 targeted drug delivery system based on glioblastoma homing peptide A2b11","authors":"Liwen Chen , Chao Shang , Yang Hong , Hui Zhang","doi":"10.1016/j.mtbio.2026.102823","DOIUrl":"10.1016/j.mtbio.2026.102823","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a highly aggressive brain tumor that offers few treatment options. Current therapeutic approaches face challenges such as poor drug delivery precision, low accumulation at tumor sites, and significant toxicity to normal tissues. To address these issues, this study designed a targeted drug delivery platform by modifying liposomes with the tumor-homing peptide A2b11, which specifically binds to the GBM-associated antigen IL13RA2. A2b11-liposomes loaded with sodium fluorescein (FLA) and A2b11-liposomes loaded with temozolomide (TLA) were evaluated for their anti-GBM effects. In vitro, studies demonstrated that A2b11-modified liposomes significantly enhanced accumulation in GBM cells and enhanced their anti-GBM efficacy compared to unmodified liposomes. In vivo, experiments using xenograft tumor mouse models showed that the targeted drug delivery platform exhibited good biocompatibility and in vivo safety. Compared to other organs, FLA demonstrated significantly higher accumulation at tumor sites, showcasing its potential for targeted therapy and enabling assessment of its effects on inducing apoptosis and inhibiting angiogenesis. Additionally, TLA induced GBM cell apoptosis and reduced tumor angiogenesis, highlighting its significant potential in inhibiting GBM tumor growth. The A2b11 peptide-modified liposomal system developed in this study represents a promising platform for GBM-targeted therapy. Further research and development of this platform could lay the groundwork for its future clinical application.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102823"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024536","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 : 2026-04-01Epub Date: 2026-02-04DOI: 10.1016/j.mtbio.2026.102890
Hongyun Xuan , Zihao Liu , Keyu Lu , Yao Chen , Haonan Gu , Biyun Li , Jingjun Sun , Yan Jin , Yumin Yang , Huihua Yuan
Diabetic wound repair remains a formidable clinical challenge due to impaired healing and heightened infection risks associated with conventional sutures. To address these limitations, this study introduces a novel injectable, self-healing, and antibacterial polysaccharide hydrogel (PGHAA), synthesized from borated peach gum and oxime-modified hyaluronic acid. By leveraging dynamic boronic ester bonds and metal coordination, PGHAA demonstrates enhanced tissue adhesion, self-healing capabilities, and antibacterial activity with immunomodulatory capacity to reprogram chronic wounds into a regenerative state. The incorporation of arginine as a cross-linking agent further improves both biocompatibility and functional performance. In vitro and in vivo evaluations indicate that PGHAA facilitates rapid hemostasis, robust tissue adhesion, and macrophage polarization toward a pro-regenerative phenotype, resulting in accelerated diabetic wound healing. Using an in vivo study with chronic diabetic skin we demonstrated that PGHAA induced wound healing via modulation of IL-17/NF-κB signaling—a pathway repurposed from its classical inflammatory role to drive tissue regeneration. This work redefines diabetic wound therapy by introducing a first-in-class hydrogel that leverages immune modulation for tissue repair, offering a transformative solution for regenerative medicine.
{"title":"Immunomodulatory hydrogel reprograms IL-17/NF-κB signaling to drive regeneration in diabetic wounds","authors":"Hongyun Xuan , Zihao Liu , Keyu Lu , Yao Chen , Haonan Gu , Biyun Li , Jingjun Sun , Yan Jin , Yumin Yang , Huihua Yuan","doi":"10.1016/j.mtbio.2026.102890","DOIUrl":"10.1016/j.mtbio.2026.102890","url":null,"abstract":"<div><div>Diabetic wound repair remains a formidable clinical challenge due to impaired healing and heightened infection risks associated with conventional sutures. To address these limitations, this study introduces a novel injectable, self-healing, and antibacterial polysaccharide hydrogel (PGHAA), synthesized from borated peach gum and oxime-modified hyaluronic acid. By leveraging dynamic boronic ester bonds and metal coordination, PGHAA demonstrates enhanced tissue adhesion, self-healing capabilities, and antibacterial activity with immunomodulatory capacity to reprogram chronic wounds into a regenerative state. The incorporation of arginine as a cross-linking agent further improves both biocompatibility and functional performance. In vitro and in vivo evaluations indicate that PGHAA facilitates rapid hemostasis, robust tissue adhesion, and macrophage polarization toward a pro-regenerative phenotype, resulting in accelerated diabetic wound healing. Using an in vivo study with chronic diabetic skin we demonstrated that PGHAA induced wound healing via modulation of IL-17/NF-κB signaling—a pathway repurposed from its classical inflammatory role to drive tissue regeneration. This work redefines diabetic wound therapy by introducing a first-in-class hydrogel that leverages immune modulation for tissue repair, offering a transformative solution for regenerative medicine.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102890"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170412","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 : 2026-04-01Epub 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":"2026-04-01","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 : 2026-04-01Epub Date: 2026-01-15DOI: 10.1016/j.mtbio.2026.102805
Fei Wu , Nashwa Amin , Xia Yuan , Azhar Badry Hussain , Irum Naz Abbasi , Javaria Sundus , Keming Shan , Yang Yang , Suhong Ye , Qining Yang , Marong Fang
Stroke remains a leading cause of global mortality and long-term disability. Chitosan-based nitric oxide nanoparticles (CS-NO), a novel injectable hydrogel, demonstrate protective effects in ischemia/reperfusion injury. However, the therapeutic efficacy and underlying mechanisms of CS-NO in stroke remain unclear. Here, we found that CS-NO exerted significant neuroprotective effects, as evidenced by neurofunctional assessments, along with marked reductions in neuronal apoptosis and inflammatory responses in stroke male mice models. Mechanistically, RNA-seq analysis combined with functional studies using an AAV9 delivery system revealed that the pathological interaction between HIF-1α and the MAPK pathway serves as a key driver in stroke development, which could be effectively inhibited by CS-NO administration. Notably, combination therapy involving CS-NO with either HIF-1α or TLR4 inhibitors showed superior neurological outcomes compared to monotherapy in stroke male mice. Collectively, CS-NO's neuroprotection may stem from disrupting HIF-1α-MAPK crosstalk following stroke, suggesting the need for translational studies to further validate its clinical potential. This study introduces a novel chitosan-based nitric oxide (NO)-releasing hydrogel (CS-NO) designed for responsive release in the ischemic microenvironment, offering a targeted and sustained therapeutic approach distinct from bolus NO donors.
{"title":"CS-NO releasing hydrogel protects against neuron apoptosis and inflammation through suppressing the HIF-1α and MAPK pathway in stroke","authors":"Fei Wu , Nashwa Amin , Xia Yuan , Azhar Badry Hussain , Irum Naz Abbasi , Javaria Sundus , Keming Shan , Yang Yang , Suhong Ye , Qining Yang , Marong Fang","doi":"10.1016/j.mtbio.2026.102805","DOIUrl":"10.1016/j.mtbio.2026.102805","url":null,"abstract":"<div><div>Stroke remains a leading cause of global mortality and long-term disability. Chitosan-based nitric oxide nanoparticles (CS-NO), a novel injectable hydrogel, demonstrate protective effects in ischemia/reperfusion injury. However, the therapeutic efficacy and underlying mechanisms of CS-NO in stroke remain unclear. Here, we found that CS-NO exerted significant neuroprotective effects, as evidenced by neurofunctional assessments, along with marked reductions in neuronal apoptosis and inflammatory responses in stroke male mice models. Mechanistically, RNA-seq analysis combined with functional studies using an AAV9 delivery system revealed that the pathological interaction between HIF-1α and the MAPK pathway serves as a key driver in stroke development, which could be effectively inhibited by CS-NO administration. Notably, combination therapy involving CS-NO with either HIF-1α or TLR4 inhibitors showed superior neurological outcomes compared to monotherapy in stroke male mice. Collectively, CS-NO's neuroprotection may stem from disrupting HIF-1α-MAPK crosstalk following stroke, suggesting the need for translational studies to further validate its clinical potential. This study introduces a novel chitosan-based nitric oxide (NO)-releasing hydrogel (CS-NO) designed for responsive release in the ischemic microenvironment, offering a targeted and sustained therapeutic approach distinct from bolus NO donors.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102805"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024397","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 : 2026-04-01Epub Date: 2026-01-24DOI: 10.1016/j.mtbio.2026.102840
Shu Feng , Ying Xuan , Hong Jin , Meng Cui , Xinyue Meng , Jun Liao , Jianwei Feng
Hepatocellular carcinoma (HCC) remains a formidable challenge due to profound heterogeneity, recurrence, and pervasive therapeutic resistance, creating a significant unmet clinical need. Engineered nanozymes, nanomaterials with intrinsic catalytic activities, have emerged as a transformative paradigm. Unlike passive nanocarriers, nanozymes function as active therapeutic agents. Their prowess is predicated on catalytically manipulating the tumor microenvironment (TME), enabling localized ROS generation, inducing regulated cell death, and remodeling the immunosuppressive TME. This review systematically delineates the principles and potential of nanozyme strategies for HCC, focusing on catalytic therapy, nanozyme-enhanced immunotherapy, photothermal therapy, and integrated combination platforms, highlighting their capacity for synergistic antitumor effects. The review also critically discusses formidable challenges spanning metabolic heterogeneity, TME-driven immunosuppression, and biocompatibility hurdles that impede clinical translation. This work provides critical insights for the rational design of next-generation nanozymes and accelerating their integration into future multidisciplinary HCC treatment frameworks.
{"title":"Nanozyme for precision treatment of hepatocellular carcinoma","authors":"Shu Feng , Ying Xuan , Hong Jin , Meng Cui , Xinyue Meng , Jun Liao , Jianwei Feng","doi":"10.1016/j.mtbio.2026.102840","DOIUrl":"10.1016/j.mtbio.2026.102840","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains a formidable challenge due to profound heterogeneity, recurrence, and pervasive therapeutic resistance, creating a significant unmet clinical need. Engineered nanozymes, nanomaterials with intrinsic catalytic activities, have emerged as a transformative paradigm. Unlike passive nanocarriers, nanozymes function as active therapeutic agents. Their prowess is predicated on catalytically manipulating the tumor microenvironment (TME), enabling localized ROS generation, inducing regulated cell death, and remodeling the immunosuppressive TME. This review systematically delineates the principles and potential of nanozyme strategies for HCC, focusing on catalytic therapy, nanozyme-enhanced immunotherapy, photothermal therapy, and integrated combination platforms, highlighting their capacity for synergistic antitumor effects. The review also critically discusses formidable challenges spanning metabolic heterogeneity, TME-driven immunosuppression, and biocompatibility hurdles that impede clinical translation. This work provides critical insights for the rational design of next-generation nanozymes and accelerating their integration into future multidisciplinary HCC treatment frameworks.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102840"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079015","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 : 2026-04-01Epub Date: 2026-01-21DOI: 10.1016/j.mtbio.2026.102811
Yongkang Lai , Yongliang Ouyang , Xiaojing Yin , Tao Yu , Jianhua Wan , Xueyang Li , Yi Hu , Xu Shu , Huan Wang
Chronic pancreatitis (CP) is a lifelong progressive fibrotic inflammatory disorder for which no effective cure is currently available. Persistent and recurrent inflammatory stimulation induced by reactive oxygen species (ROS) is a key driver of pancreatic fibrogenesis, making oxidative stress a promising therapeutic target to halt disease progression. In this study, we developed a nanosystem, HC@CeMOF, consisting of a small-sized cerium-based metal–organic framework (CeMOF) core loaded with curcumin and coated with hyaluronic acid (HA), enabling precise targeting of inflamed pancreatic tissue. HC@CeMOF exhibits a small-sized particle size along with favorable cellular and biological safety profiles. Once administered in vivo, the nanosystem exploits the specific binding affinity of HA to CD44 receptors on macrophages to selectively accumulate at inflamed pancreatic sites. Subsequently, the cerium-based nanozyme efficiently scavenges ROS through the reversible redox cycling between Ce3+ and Ce4+, while the slow release of curcumin further suppresses the NF-κB signaling pathway and modulates inflammatory cytokine levels, thereby achieving synergistic anti-inflammatory and antioxidant effects. Collectively, these mechanisms substantially attenuate CP progression. This targeted ROS-scavenging and anti-inflammatory strategy holds promise as an alternative therapeutic approach for chronic pancreatitis.
{"title":"Engineered targeted Ce-based MOF nanozymes for ROS scavenging and inflammatory Reprogramming in chronic pancreatitis","authors":"Yongkang Lai , Yongliang Ouyang , Xiaojing Yin , Tao Yu , Jianhua Wan , Xueyang Li , Yi Hu , Xu Shu , Huan Wang","doi":"10.1016/j.mtbio.2026.102811","DOIUrl":"10.1016/j.mtbio.2026.102811","url":null,"abstract":"<div><div>Chronic pancreatitis (CP) is a lifelong progressive fibrotic inflammatory disorder for which no effective cure is currently available. Persistent and recurrent inflammatory stimulation induced by reactive oxygen species (ROS) is a key driver of pancreatic fibrogenesis, making oxidative stress a promising therapeutic target to halt disease progression. In this study, we developed a nanosystem, HC@CeMOF, consisting of a small-sized cerium-based metal–organic framework (CeMOF) core loaded with curcumin and coated with hyaluronic acid (HA), enabling precise targeting of inflamed pancreatic tissue. HC@CeMOF exhibits a small-sized particle size along with favorable cellular and biological safety profiles. Once administered <em>in vivo</em>, the nanosystem exploits the specific binding affinity of HA to CD44 receptors on macrophages to selectively accumulate at inflamed pancreatic sites. Subsequently, the cerium-based nanozyme efficiently scavenges ROS through the reversible redox cycling between Ce<sup>3+</sup> and Ce<sup>4+</sup>, while the slow release of curcumin further suppresses the NF-κB signaling pathway and modulates inflammatory cytokine levels, thereby achieving synergistic anti-inflammatory and antioxidant effects. Collectively, these mechanisms substantially attenuate CP progression. This targeted ROS-scavenging and anti-inflammatory strategy holds promise as an alternative therapeutic approach for chronic pancreatitis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102811"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079017","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 : 2026-04-01Epub Date: 2026-01-21DOI: 10.1016/j.mtbio.2026.102804
Xiaoxin Yang , Mi Huang , Tianyi Pang , Dong Zhong , Hong Liu , Xiang Chen , Jun Liu , Yu Wen
The low infiltration of pro-inflammatory immune cells and the sustained activation of multiple immunosuppressive signaling pathways in melanoma significantly limit the efficacy of clinical immunotherapy. Therefore, developing an effective immunostimulant with reversing the immunosuppressive tumor microenvironment (TME) is of great significance for improving melanoma immunotherapy. Herein, a degradable metalloimmunostimulant (PurpN/Mn@PEG) is developed for immunotherapy targeting immunosuppressive melanoma. The PurpN/Mn@PEG NPs are fabricated by coordination-driven self-assembly of purpurin and Mn2+, followed by polyethylene glycol (PEG) modification. PurpN/Mn@PEG dissociates in acidic pH and high glutathione TME, releasing PurpN and Mn2+. The nanoparticle exhibits peroxidase-/oxidase-like activity, generating a reactive oxygen species (ROS) storm that induces immunogenic cell death. PurpN/Mn@PEG amplifies ROS via H2O2 production through phenolic oxidation, enhances TNF-α secretion via CCAAT/enhancer-binding protein beta (CEBPB) upregulation, and sensitizes cGAS-STING pathway, synergistically boosting melanoma immunotherapy. In vivo experiments demonstrated that this purpurin-based metalloimmunostimulant exhibits remarkable therapeutic efficacy with an 87.8 % tumor growth inhibition rate in B16-F10 melanoma-bearing mice by activating multiple immune pathways, thereby effectively augmenting melanoma immunotherapy. This study provides an innovative therapeutic strategy that effectively reprograms the immunosuppressive TME to potentiate melanoma immunotherapy.
{"title":"A purpurin-based metalloimmunostimulant amplifies ROS and modulates STING/TNF-α axis to potentiate melanoma immunotherapy","authors":"Xiaoxin Yang , Mi Huang , Tianyi Pang , Dong Zhong , Hong Liu , Xiang Chen , Jun Liu , Yu Wen","doi":"10.1016/j.mtbio.2026.102804","DOIUrl":"10.1016/j.mtbio.2026.102804","url":null,"abstract":"<div><div>The low infiltration of pro-inflammatory immune cells and the sustained activation of multiple immunosuppressive signaling pathways in melanoma significantly limit the efficacy of clinical immunotherapy. Therefore, developing an effective immunostimulant with reversing the immunosuppressive tumor microenvironment (TME) is of great significance for improving melanoma immunotherapy. Herein, a degradable metalloimmunostimulant (PurpN/Mn@PEG) is developed for immunotherapy targeting immunosuppressive melanoma. The PurpN/Mn@PEG NPs are fabricated by coordination-driven self-assembly of purpurin and Mn<sup>2+</sup>, followed by polyethylene glycol (PEG) modification. PurpN/Mn@PEG dissociates in acidic pH and high glutathione TME, releasing PurpN and Mn<sup>2+</sup>. The nanoparticle exhibits peroxidase-/oxidase-like activity, generating a reactive oxygen species (ROS) storm that induces immunogenic cell death. PurpN/Mn@PEG amplifies ROS via H<sub>2</sub>O<sub>2</sub> production through phenolic oxidation, enhances TNF-α secretion via CCAAT/enhancer-binding protein beta (CEBPB) upregulation, and sensitizes cGAS-STING pathway, synergistically boosting melanoma immunotherapy. In vivo experiments demonstrated that this purpurin-based metalloimmunostimulant exhibits remarkable therapeutic efficacy with an 87.8 % tumor growth inhibition rate in B16-F10 melanoma-bearing mice by activating multiple immune pathways, thereby effectively augmenting melanoma immunotherapy. This study provides an innovative therapeutic strategy that effectively reprograms the immunosuppressive TME to potentiate melanoma immunotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102804"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165995","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 : 2026-04-01Epub Date: 2026-01-21DOI: 10.1016/j.mtbio.2026.102817
Jianan Yu , Shaosheng Jia , Rongbang Sun , Tong Zhang , Xinyuan Cai , Manli Song , Lan Chen , Han Lin , Shaokang Guan
Frequent tumor recurrence and postoperative bacterial infections after osteosarcoma surgery have increased the demand for advanced bone implants. Although magnesium and its alloys are considered promising candidates for next-generation bone implants, their clinical application remains limited due to inadequate corrosion resistance. In this work, manganese oxide (MnOx) nano-coatings with varying Mn3+/Mn2+ ratios were fabricated on the surface of ZE21C alloys via heat treatment, effectively enhancing corrosion resistance. The MnOx nano-coatings consisted of multiple semiconductors with different Mn3+/Mn2+ ratios, and Mn2O3 with a narrower band gap became the dominant phase with heat treatment, resulting in a significant improvement in the photothermal conversion performance. In vivo and in vitro experiments demonstrated that samples with higher Mn3+/Mn2+ ratios disrupted redox homeostasis, inducing lipid peroxidation of biological membranes. Additionally, valence electrons in the semiconductors could be excited by NIR irradiation to generate photogenerated carriers, forming transmembrane electron-transfer channels with adhered tumor and bacterial cells, leading to structural membrane disruption and sustained antibacterial and tumor cell ablation. Furthermore, Mg alloys modified with MnOx nano-coatings exhibited excellent biocompatibility and did not inhibit mitochondrial function of normal cells. This work provides a broader range of options and practical solutions for developing intelligent bone tissue-engineering materials for postoperative osteosarcoma.
{"title":"MnOx-armored magnesium implants for anti-osteosarcoma and biofilm eradication by charge-transfer interference","authors":"Jianan Yu , Shaosheng Jia , Rongbang Sun , Tong Zhang , Xinyuan Cai , Manli Song , Lan Chen , Han Lin , Shaokang Guan","doi":"10.1016/j.mtbio.2026.102817","DOIUrl":"10.1016/j.mtbio.2026.102817","url":null,"abstract":"<div><div>Frequent tumor recurrence and postoperative bacterial infections after osteosarcoma surgery have increased the demand for advanced bone implants. Although magnesium and its alloys are considered promising candidates for next-generation bone implants, their clinical application remains limited due to inadequate corrosion resistance. In this work, manganese oxide (MnO<sub>x</sub>) nano-coatings with varying Mn<sup>3+</sup>/Mn<sup>2+</sup> ratios were fabricated on the surface of ZE21C alloys via heat treatment, effectively enhancing corrosion resistance. The MnO<sub>x</sub> nano-coatings consisted of multiple semiconductors with different Mn<sup>3+</sup>/Mn<sup>2+</sup> ratios, and Mn<sub>2</sub>O<sub>3</sub> with a narrower band gap became the dominant phase with heat treatment, resulting in a significant improvement in the photothermal conversion performance. <em>In vivo</em> and <em>in vitro</em> experiments demonstrated that samples with higher Mn<sup>3+</sup>/Mn<sup>2+</sup> ratios disrupted redox homeostasis, inducing lipid peroxidation of biological membranes. Additionally, valence electrons in the semiconductors could be excited by NIR irradiation to generate photogenerated carriers, forming transmembrane electron-transfer channels with adhered tumor and bacterial cells, leading to structural membrane disruption and sustained antibacterial and tumor cell ablation. Furthermore, Mg alloys modified with MnO<sub>x</sub> nano-coatings exhibited excellent biocompatibility and did not inhibit mitochondrial function of normal cells. This work provides a broader range of options and practical solutions for developing intelligent bone tissue-engineering materials for postoperative osteosarcoma.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102817"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165297","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 : 2026-04-01Epub Date: 2026-01-28DOI: 10.1016/j.mtbio.2026.102850
Xiaofei Zheng , Tiaotiao Zhu , Xuanyu Lin , Pengjing Chen , Baiwei Ma , Juanfang Zhu
Periodontitis, a widespread inflammatory disease, is difficult to treat effectively due to incomplete mechanical cleaning and increasing antibiotic resistance. To overcome this issue, we developed a new covalent organic framework, THP-PE-COF, which combines aggregation-induced emission (AIE) with local asymmetric electron distribution (LAED) to enhance photodynamic therapy (PDT). The AIE unit prolongs fluorescence lifetime and inhibits charge recombination, while the electron-donating triphenylthiophene (THP) induces LAED to form local dipoles that promote oxygen adsorption and charge separation. Compared with control THP-PB-COF and THP-BPE-COF, THP-PE-COF exhibited improved light absorption, charge dynamics, and reactive oxygen species (ROS) generation. It showed strong antibacterial activity against Porphyromonas gingivalis and Fusobacterium nucleatum in vitro and demonstrated effective periodontitis treatment with decreased inflammatory responses in vivo. This work pioneered the integration of AIE and LAED in COFs, providing a promising antibiotic-free strategy for periodontal therapy.
{"title":"A synergistic strategy of AIE and electron asymmetry anchored in covalent organic frameworks for enhanced periodontitis photodynamic therapy","authors":"Xiaofei Zheng , Tiaotiao Zhu , Xuanyu Lin , Pengjing Chen , Baiwei Ma , Juanfang Zhu","doi":"10.1016/j.mtbio.2026.102850","DOIUrl":"10.1016/j.mtbio.2026.102850","url":null,"abstract":"<div><div>Periodontitis, a widespread inflammatory disease, is difficult to treat effectively due to incomplete mechanical cleaning and increasing antibiotic resistance. To overcome this issue, we developed a new covalent organic framework, THP-PE-COF, which combines aggregation-induced emission (AIE) with local asymmetric electron distribution (LAED) to enhance photodynamic therapy (PDT). The AIE unit prolongs fluorescence lifetime and inhibits charge recombination, while the electron-donating triphenylthiophene (THP) induces LAED to form local dipoles that promote oxygen adsorption and charge separation. Compared with control THP-PB-COF and THP-BPE-COF, THP-PE-COF exhibited improved light absorption, charge dynamics, and reactive oxygen species (ROS) generation. It showed strong antibacterial activity against <em>Porphyromonas gingivalis</em> and <em>Fusobacterium nucleatum in vitro</em> and demonstrated effective periodontitis treatment with decreased inflammatory responses <em>in vivo</em>. This work pioneered the integration of AIE and LAED in COFs, providing a promising antibiotic-free strategy for periodontal therapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102850"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166051","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 : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.mtbio.2026.102832
Zhaorong Ouyang , Siyu Li , Ao Zhang , Shu Ye , Wanqiu Ye , Guolei Wen , Tao Wei , Biao Cai , Houli Liu
Ganoderma lucidum polysaccharide (GLP) holds considerable promise for tumor therapy, but its clinical application is limited by its poor tumor-targeting capability. Herein, we report the development of an immunoregulatory nano-bioconjugate formed by conjugating GLPs with low-pH culture medium reprogrammed CT26 tumor cell-derived extracellular vesicle (LTEV). Specifically, 4-carboxybenzeneboronic acid (CPBA), used as an intermediate coupling agent, is conjugated with the amino group of LTEV via its carboxyl group to obtain CPBA-LTEV. GLP is then covalently linked via boric ester linkages between its hydroxyl groups and the boronic acid groups of CPBA. After systemic administration, GLP@LTEV accumulates in homologous tumor tissues derived from the LTEV parent cells, remodeling the immunosuppressive tumor microenvironment (TME) by repolarizing M2-like macrophages towards the M1 phenotype, promoting dendritic cell (DC) maturation, activating cytotoxic T lymphocytes (CTLs), and inhibiting immunosuppressive regulatory T cells (Tregs). The synergism of tumor-targeting delivery and potent immunomodulatory effects in this combined manner therefore significantly inhibits subcutaneous tumor growth and lung metastasis with minimal side effects, providing a novel combination of polysaccharide and nanovesicle for robust tumor immunotherapy.
{"title":"Ganoderma lucidum polysaccharide-decorated extracellular vesicle enables synergistical antitumor immunotherapy","authors":"Zhaorong Ouyang , Siyu Li , Ao Zhang , Shu Ye , Wanqiu Ye , Guolei Wen , Tao Wei , Biao Cai , Houli Liu","doi":"10.1016/j.mtbio.2026.102832","DOIUrl":"10.1016/j.mtbio.2026.102832","url":null,"abstract":"<div><div><em>Ganoderma lucidum</em> polysaccharide (GLP) holds considerable promise for tumor therapy, but its clinical application is limited by its poor tumor-targeting capability. Herein, we report the development of an immunoregulatory nano-bioconjugate formed by conjugating GLPs with low-pH culture medium reprogrammed CT26 tumor cell-derived extracellular vesicle (LTEV). Specifically, 4-carboxybenzeneboronic acid (CPBA), used as an intermediate coupling agent, is conjugated with the amino group of LTEV via its carboxyl group to obtain CPBA-LTEV. GLP is then covalently linked via boric ester linkages between its hydroxyl groups and the boronic acid groups of CPBA. After systemic administration, GLP@LTEV accumulates in homologous tumor tissues derived from the LTEV parent cells, remodeling the immunosuppressive tumor microenvironment (TME) by repolarizing M2-like macrophages towards the M1 phenotype, promoting dendritic cell (DC) maturation, activating cytotoxic T lymphocytes (CTLs), and inhibiting immunosuppressive regulatory T cells (Tregs). The synergism of tumor-targeting delivery and potent immunomodulatory effects in this combined manner therefore significantly inhibits subcutaneous tumor growth and lung metastasis with minimal side effects, providing a novel combination of polysaccharide and nanovesicle for robust tumor immunotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102832"},"PeriodicalIF":10.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079016","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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