Pub Date : 2026-01-08DOI: 10.1016/j.biomaterials.2026.123993
Xianting Sun , Cai Feng , Zongling Xiong , Yifei Yang , Hao Zhou , Tianming Wang , Xiaofen Wang , Shulin Liu , Sai Li , Peng Lei , Liangrong Shi , Weihua Liao
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.
{"title":"Harnessing the HMnO2 nanoparticles as the DNA injury amplifier to improve the OXA-based trans-artery infusion chemotherapy","authors":"Xianting Sun , Cai Feng , Zongling Xiong , Yifei Yang , Hao Zhou , Tianming Wang , Xiaofen Wang , Shulin Liu , Sai Li , Peng Lei , Liangrong Shi , 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 MnO<sub>2</sub> nanoparticle loaded with OXA, the PEI-HMnO<sub>2</sub>@OXA, to improve the TAIC effect of OXA. The acidic tumor microenvironment facilitated the release of OXA and triggered PEI-HMnO<sub>2</sub> to generate free radicals. When coupled with GSH depletion, this cascade culminated in significant DNA damage. Moreover, the PEI-HMnO<sub>2</sub> 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-HMnO<sub>2</sub>@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-HMnO<sub>2</sub>@OXA, providing novel insights into cancer management.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 123993"},"PeriodicalIF":12.9,"publicationDate":"2026-01-08","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}
Pub Date : 2026-01-07DOI: 10.1016/j.biomaterials.2025.123968
Yongchang Tian , Rong Zhang , Xingjun Zhao , Ian W. Hamley , Chunsheng Xiao , Li Chen
Antimicrobial hydrogels that can effectively eliminate microorganisms to accelerate wound healing have demostrated great potential in managing wound infections. However, conventional hydrogel dressings have limited contact with bacteria due to their permemnent cross-linked structure, thereby reducing their bactericidal efficiency. To address this issue, we designed and prepared a neutrophil extracellular traps (NETs) biomimetic antibacterial hydrogel (PETP gel) with enhanced bacteria contact and bactericidal efficiency through Schiff base crosslinking of antibacterial polymer PETP-NH2 and phenylboronic acid functionalized oxidized hyaluronic acid (OHA-PBA). The obtained PETP gel exhibited a NETs-mimicking dynamic filamentous network structure, which, in combination with the interaction between phenylboronic acid in OHA-PBA and lipopolysaccharides in bacterial surface, ultimately led to enhanced bacteria contact and bactericidal efficiency. In vivo experiments showed that PETP gel could accelerate healing in treatment of purulent subcutaneous infection, full-thickness wound infection, and deep second-degree burn infection, showing promising use as an antibacterial care dressing.
{"title":"A biomietic filamentous hydrogel with enhanced bacteria contact and bactericidal efficiency for the treatment of various skin infections","authors":"Yongchang Tian , Rong Zhang , Xingjun Zhao , Ian W. Hamley , Chunsheng Xiao , Li Chen","doi":"10.1016/j.biomaterials.2025.123968","DOIUrl":"10.1016/j.biomaterials.2025.123968","url":null,"abstract":"<div><div>Antimicrobial hydrogels that can effectively eliminate microorganisms to accelerate wound healing have demostrated great potential in managing wound infections. However, conventional hydrogel dressings have limited contact with bacteria due to their permemnent cross-linked structure, thereby reducing their bactericidal efficiency. To address this issue, we designed and prepared a neutrophil extracellular traps (NETs) biomimetic antibacterial hydrogel (PETP gel) with enhanced bacteria contact and bactericidal efficiency through Schiff base crosslinking of antibacterial polymer PETP-NH<sub>2</sub> and phenylboronic acid functionalized oxidized hyaluronic acid (OHA-PBA). The obtained PETP gel exhibited a NETs-mimicking dynamic filamentous network structure, which, in combination with the interaction between phenylboronic acid in OHA-PBA and lipopolysaccharides in bacterial surface, ultimately led to enhanced bacteria contact and bactericidal efficiency. <em>In vivo</em> experiments showed that PETP gel could accelerate healing in treatment of purulent subcutaneous infection, full-thickness wound infection, and deep second-degree burn infection, showing promising use as an antibacterial care dressing.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"330 ","pages":"Article 123968"},"PeriodicalIF":12.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975838","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 : 2026-01-06DOI: 10.1016/j.biomaterials.2026.123992
Shi Chen , Yibo Du , Chenxu Zhu , Chuang Li , Xingliang Liu , Lixin Liu , Yongming Chen
Excessive accumulation of cell-free DNA (cfDNA) has been identified as a primary pathogenic factor in autoimmune diseases. The circulating deoxyribonuclease (DNase) maintaining cfDNA homeostasis is suppressed, and thus exogenous DNase has been applied to degrade cfDNA for inflammation control. However, in pathological states, cfDNA and cationic endogenous peptide (e.g., LL37) form immune complexes (ICs), which not only weaken DNase efficacy but also facilitate immune cell internalization to induce an inflammatory response. With LL37-DNA as a model IC, here we found that the LL37 occupancy not only sterically hinders cfDNA's access to the catalytic sites but also induces deactivation of DNase via formation of ternary complexes (LL37-DNA-DNase I). This transition critically impairs the activity of DNase I within LL37-rich inflammatory microenvironments. Thus, we postulated that heparin, a clinically approved anionic glycosaminoglycan, could destruct the ICs and liberate cfDNAs, restoring their susceptibility to degradation. Indeed, we found that a combination of heparin and DNase I facilitates the DNA degradation and inhibits the ICs-mediated TLR9 activation in vitro. However, the therapeutic outcome observed in rheumatoid arthritis (RA) model was still suboptimal, attributed to the short plasma half-life of DNase. To validate this, we engineered a DNase nanoparticle (DNase@TANP) capable of sustained release of the enzyme. Consequently, the sequential administration of heparin and DNase@TANP (with a 30-min interval) to RA model demonstrated a synergistic cfDNA degradation efficiency, effectively suppressing Toll-like receptor (TLR) mediated inflammatory pathways and ameliorating joint inflammation. This strategy, leveraging clinically approved agents for cfDNA clearance, establishes a promising therapeutic paradigm for cfDNA-associated autoimmune disorders.
游离DNA （cfDNA）的过度积累已被确定为自身免疫性疾病的主要致病因素。维持cfDNA稳态的循环脱氧核糖核酸酶（循环脱氧核糖核酸酶）被抑制，因此外源性dna酶被用于降解cfDNA以控制炎症。然而，在病理状态下，cfDNA与阳离子内源性肽（如LL37）形成免疫复合物（ic），不仅削弱DNase的功效，而且促进免疫细胞内化，诱导炎症反应。以LL37- dna为模型IC，我们发现LL37的占用不仅在空间上阻碍cfDNA进入催化位点，而且通过形成三元配合物（LL37- dna -DNase I）诱导dna酶失活。这种转变严重损害了富含ll37的炎症微环境中DNase I的活性。因此，我们假设肝素，一种临床批准的阴离子糖胺聚糖，可以破坏ic并释放cfdna，恢复其降解易感性。事实上，我们发现肝素和DNA酶I的结合促进了DNA降解，并抑制了ics介导的TLR9的体外激活。然而，在类风湿关节炎（RA）模型中观察到的治疗结果仍然不理想，这是由于dna酶的血浆半衰期较短。为了验证这一点，我们设计了一种能够持续释放酶的dna酶纳米颗粒（DNase@TANP）。因此，依次给药肝素和DNase@TANP（间隔30分钟）对RA模型显示协同cfDNA降解效率，有效抑制toll样受体（TLR）介导的炎症途径并改善关节炎症。该策略利用临床批准的cfDNA清除药物，为cfDNA相关自身免疫性疾病建立了一个有希望的治疗范例。
{"title":"Stripping cell-free DNA from its immune complex is essential for inflammation control using DNase I","authors":"Shi Chen , Yibo Du , Chenxu Zhu , Chuang Li , Xingliang Liu , Lixin Liu , Yongming Chen","doi":"10.1016/j.biomaterials.2026.123992","DOIUrl":"10.1016/j.biomaterials.2026.123992","url":null,"abstract":"<div><div>Excessive accumulation of cell-free DNA (cfDNA) has been identified as a primary pathogenic factor in autoimmune diseases. The circulating deoxyribonuclease (DNase) maintaining cfDNA homeostasis is suppressed, and thus exogenous DNase has been applied to degrade cfDNA for inflammation control. However, in pathological states, cfDNA and cationic endogenous peptide (<em>e.g.</em>, LL37) form immune complexes (ICs), which not only weaken DNase efficacy but also facilitate immune cell internalization to induce an inflammatory response. With LL37-DNA as a model IC, here we found that the LL37 occupancy not only sterically hinders cfDNA's access to the catalytic sites but also induces deactivation of DNase <em>via</em> formation of ternary complexes (LL37-DNA-DNase I). This transition critically impairs the activity of DNase I within LL37-rich inflammatory microenvironments. Thus, we postulated that heparin, a clinically approved anionic glycosaminoglycan, could destruct the ICs and liberate cfDNAs, restoring their susceptibility to degradation. Indeed, we found that a combination of heparin and DNase I facilitates the DNA degradation and inhibits the ICs-mediated TLR9 activation <em>in vitro</em>. However, the therapeutic outcome observed in rheumatoid arthritis (RA) model was still suboptimal, attributed to the short plasma half-life of DNase. To validate this, we engineered a DNase nanoparticle (DNase@TANP) capable of sustained release of the enzyme. Consequently, the sequential administration of heparin and DNase@TANP (with a 30-min interval) to RA model demonstrated a synergistic cfDNA degradation efficiency, effectively suppressing Toll-like receptor (TLR) mediated inflammatory pathways and ameliorating joint inflammation. This strategy, leveraging clinically approved agents for cfDNA clearance, establishes a promising therapeutic paradigm for cfDNA-associated autoimmune disorders.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123992"},"PeriodicalIF":12.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950967","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 : 2026-01-06DOI: 10.1016/j.biomaterials.2025.123976
Qiaofeng Li , Zhisheng Xiao , Bo Liu , Yuchun Xu , Chunjie Wang , Mingkang Li , Yuzhe Wu , Chenxi Yin , Wenzhuo Yu , Zhuang Liu , Yu Chao
Chimeric antigen receptor (CAR)-T cell therapy while demonstrating remarkable efficacies in treating hematologic malignancies, has encountered challenges in solid tumor treatment, partly due to the limited intratumoral infiltration of effective immune cells and thus inefficient interactions between different immune cell types inside those tumors. Herein, we develop an injectable scaffold based on hydrogel microparticles (HMPs) with opposite charges to replicate tertiary lymphoid structures (TLSs) within the tumor microenvironment. With encapsulation of immune-stimulating cytokines inside HMPs and loading of both T cells and B cells between HMPs in the scaffold, the artificial TLSs after intratumoral injection could not only serve as a depot of immunostimulants, but also promote intercellular interactions between B and T lymphocytes to support continuous T cell expansion and activation. As demonstrated in several tumor models, our artificial TLSs loaded with both CAR-T cells and B cells after intratumoral injection could not only effectively suppress local tumors, but also present remarkable abscopal effects to inhibit distant tumors, presenting greatly enhanced therapeutic performance compared to conventional CAR-T therapy. Our work thus presents a novel strategy to improve the efficacy of T-cell-therapies against solid tumors based on immune-activating cell-loaded injectable hydrogel scaffold as artificial TLSs.
{"title":"Self-assembled microparticle hydrogel scaffolds to construct artificial tertiary lymphoids for enhanced CAR-T cell therapy against solid tumors","authors":"Qiaofeng Li , Zhisheng Xiao , Bo Liu , Yuchun Xu , Chunjie Wang , Mingkang Li , Yuzhe Wu , Chenxi Yin , Wenzhuo Yu , Zhuang Liu , Yu Chao","doi":"10.1016/j.biomaterials.2025.123976","DOIUrl":"10.1016/j.biomaterials.2025.123976","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-T cell therapy while demonstrating remarkable efficacies in treating hematologic malignancies, has encountered challenges in solid tumor treatment, partly due to the limited intratumoral infiltration of effective immune cells and thus inefficient interactions between different immune cell types inside those tumors. Herein, we develop an injectable scaffold based on hydrogel microparticles (HMPs) with opposite charges to replicate tertiary lymphoid structures (TLSs) within the tumor microenvironment. With encapsulation of immune-stimulating cytokines inside HMPs and loading of both T cells and B cells between HMPs in the scaffold, the artificial TLSs after intratumoral injection could not only serve as a depot of immunostimulants, but also promote intercellular interactions between B and T lymphocytes to support continuous T cell expansion and activation. As demonstrated in several tumor models, our artificial TLSs loaded with both CAR-T cells and B cells after intratumoral injection could not only effectively suppress local tumors, but also present remarkable abscopal effects to inhibit distant tumors, presenting greatly enhanced therapeutic performance compared to conventional CAR-T therapy. Our work thus presents a novel strategy to improve the efficacy of T-cell-therapies against solid tumors based on immune-activating cell-loaded injectable hydrogel scaffold as artificial TLSs.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123976"},"PeriodicalIF":12.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922235","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2026.123988
Yanan Zhao , Ting Li , Yao Yao , Shujuan Xue , Tao Xu , Shuqi Mi , Dazhao Li , Xiaolei Tang , Feng Zhi , Dawei Ding , Huabing Chen
Reactive oxygen species (ROS)-based antitumor compounds show great promise in cancer treatments such as chemodynamic therapy (CDT) and photodynamic therapy (PDT), but are severely restricted by both endogenous antioxidants and hydrogen peroxide (H2O2). Here, we synthesize bidirectionally H2O2-suppliable and antioxidant-consumable copper peroxide (CuO2) nanoparticles for CDT/PDT-synergized immunotherapy against aggressive triple-negative breast cancers (TNBCs). The CuO2 nanoparticles are established to afford pH-responsive decomposition into H2O2 and Cu2+, followed by the reduction into Cu+ by glutathione and subsequent catalysis reaction of H2O2 into highly reactive ·OH, thus yielding CDT-mediated cell injury. Meanwhile, the glutathione consumption from the nanoparticles attenuates their ROS scavenging to promote singlet oxygen generation of co-assembled indocyanine green upon light exposure, thereby amplifying PDT-based cell damage. Moreover, the dully enhanced CDT/PDT damages of the nanoparticles provoke potent immunogenic cell death that further synergizes with immune checkpoint inhibitor via relieving indoleamine 2,3-dioxygenase 1-mediated immunosuppression, thus amplifying immunotherapeutic efficacy against primary, distant and metastatic TNBCs. This work provides valuable insights into nanomedicines for synergistic cancer therapy.
{"title":"Bidirectionally H2O2-suppliable and antioxidant-consumable copper peroxide nanoparticles for photochemodynamic immunotherapy","authors":"Yanan Zhao , Ting Li , Yao Yao , Shujuan Xue , Tao Xu , Shuqi Mi , Dazhao Li , Xiaolei Tang , Feng Zhi , Dawei Ding , Huabing Chen","doi":"10.1016/j.biomaterials.2026.123988","DOIUrl":"10.1016/j.biomaterials.2026.123988","url":null,"abstract":"<div><div>Reactive oxygen species (ROS)-based antitumor compounds show great promise in cancer treatments such as chemodynamic therapy (CDT) and photodynamic therapy (PDT), but are severely restricted by both endogenous antioxidants and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Here, we synthesize bidirectionally H<sub>2</sub>O<sub>2</sub>-suppliable and antioxidant-consumable copper peroxide (CuO<sub>2</sub>) nanoparticles for CDT/PDT-synergized immunotherapy against aggressive triple-negative breast cancers (TNBCs). The CuO<sub>2</sub> nanoparticles are established to afford pH-responsive decomposition into H<sub>2</sub>O<sub>2</sub> and Cu<sup>2+</sup>, followed by the reduction into Cu<sup>+</sup> by glutathione and subsequent catalysis reaction of H<sub>2</sub>O<sub>2</sub> into highly reactive ·OH, thus yielding CDT-mediated cell injury. Meanwhile, the glutathione consumption from the nanoparticles attenuates their ROS scavenging to promote singlet oxygen generation of co-assembled indocyanine green upon light exposure, thereby amplifying PDT-based cell damage. Moreover, the dully enhanced CDT/PDT damages of the nanoparticles provoke potent immunogenic cell death that further synergizes with immune checkpoint inhibitor via relieving indoleamine 2,3-dioxygenase 1-mediated immunosuppression, thus amplifying immunotherapeutic efficacy against primary, distant and metastatic TNBCs. This work provides valuable insights into nanomedicines for synergistic cancer therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123988"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958296","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2026.123990
Qiwei Yang , Minghao Li , Haoxiang Chen , Ying Li , Xinyuan Zhang , Yuan Gao , Chengyu Zhang , Jiuping Wu , Shuijun Zhang , Xinzhi Sun
Bone is one of the most common sites for tumor metastasis. The "seed-and-soil" relationship renders bone tissue a favorable microenvironment for the growth of circulating tumor cells. While immunotherapies, particularly immune checkpoint blockade (ICB), have achieved breakthroughs in primary solid tumors, bone metastases often respond poorly to ICB treatment. Herein, we developed an enzyme-loaded, self-cascading nanoreactor (mCL) that integrates a CaO2 core and l-Arginine (L-Arg) with iNOS-rich macrophage membranes. This design ensures efficient tumor targeting and, upon acid-triggered decomposition, initiates a self-reinforcing cycle of Ca2+ overload and nitric oxide (NO), reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Upon targeted accumulation and penetration in tumors, CaO2 undergoes reactive decomposition in the acidic tumor microenvironment (TME), releasing Ca2+, H2O2, and L-Arg. Subsequently, membrane derived iNOS cooperates with H2O2 to catalyze the conversion of L-Arg into NO, successfully overcoming the limitation of insufficient NO production within tumor cells. NO further enhances intracellular Ca2+ accumulation and reacts with ROS to generate highly cytotoxic RNS. These self-amplifying cascading reactions activate caspase-3/gasdermin E (GSDME)-dependent pyroptosis and the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, promoting dendritic cell maturation and T cell activation, thereby remodeling the immunosuppressive TME. When used in combination with ICB, mCL significantly inhibits the growth and recurrence of hepatocellular carcinoma spinal metastasis (HCC-SM) while establishing long-lasting immune memory, providing a promising new strategy for the immunotherapy of HCC-SM.
骨是肿瘤最常见的转移部位之一。这种“种子与土壤”的关系使骨组织成为循环肿瘤细胞生长的有利微环境。虽然免疫疗法，特别是免疫检查点阻断（ICB），在原发性实体瘤中取得了突破，但骨转移瘤对ICB治疗的反应往往很差。在此，我们开发了一种酶负载的自级联纳米反应器（mCL），该反应器将CaO2核心和l-精氨酸（L-Arg）与富含inos的巨噬细胞膜结合在一起。这种设计确保了有效的肿瘤靶向，并在酸触发分解后，启动Ca2+过载和一氧化氮（NO）、活性氧（ROS）和活性氮（RNS）生成的自我强化循环。CaO2在肿瘤中靶向积累和渗透后，在酸性肿瘤微环境（TME）中进行反应性分解，释放Ca2+、H2O2和L-Arg。随后，膜源性iNOS与H2O2协同催化L-Arg转化为NO，成功克服了肿瘤细胞内NO生成不足的限制。NO进一步增强细胞内Ca2+积累，并与ROS反应产生高细胞毒性RNS。这些自扩增级联反应激活caspase-3/gasdermin E （GSDME）依赖性焦亡和环GMP-AMP合成酶刺激干扰素基因（cGAS-STING）通路，促进树突状细胞成熟和T细胞活化，从而重塑免疫抑制的TME。mCL与ICB联合使用时，可显著抑制肝癌脊柱转移（HCC-SM）的生长和复发，同时建立持久的免疫记忆，为HCC-SM的免疫治疗提供了一种有希望的新策略。
{"title":"Bioinspired enzyme-catalytic nanoreactor enhances immunotherapy for spinal metastases by activating pyroptosis and the cGAS-STING pathway","authors":"Qiwei Yang , Minghao Li , Haoxiang Chen , Ying Li , Xinyuan Zhang , Yuan Gao , Chengyu Zhang , Jiuping Wu , Shuijun Zhang , Xinzhi Sun","doi":"10.1016/j.biomaterials.2026.123990","DOIUrl":"10.1016/j.biomaterials.2026.123990","url":null,"abstract":"<div><div>Bone is one of the most common sites for tumor metastasis. The \"seed-and-soil\" relationship renders bone tissue a favorable microenvironment for the growth of circulating tumor cells. While immunotherapies, particularly immune checkpoint blockade (ICB), have achieved breakthroughs in primary solid tumors, bone metastases often respond poorly to ICB treatment. Herein, we developed an enzyme-loaded, self-cascading nanoreactor (mCL) that integrates a CaO<sub>2</sub> core and <span>l</span>-Arginine (L-Arg) with iNOS-rich macrophage membranes. This design ensures efficient tumor targeting and, upon acid-triggered decomposition, initiates a self-reinforcing cycle of Ca<sup>2+</sup> overload and nitric oxide (NO), reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Upon targeted accumulation and penetration in tumors, CaO<sub>2</sub> undergoes reactive decomposition in the acidic tumor microenvironment (TME), releasing Ca<sup>2+</sup>, H<sub>2</sub>O<sub>2</sub>, and L-Arg. Subsequently, membrane derived iNOS cooperates with H<sub>2</sub>O<sub>2</sub> to catalyze the conversion of L-Arg into NO, successfully overcoming the limitation of insufficient NO production within tumor cells. NO further enhances intracellular Ca<sup>2+</sup> accumulation and reacts with ROS to generate highly cytotoxic RNS. These self-amplifying cascading reactions activate caspase-3/gasdermin E (GSDME)-dependent pyroptosis and the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway, promoting dendritic cell maturation and T cell activation, thereby remodeling the immunosuppressive TME. When used in combination with ICB, mCL significantly inhibits the growth and recurrence of hepatocellular carcinoma spinal metastasis (HCC-SM) while establishing long-lasting immune memory, providing a promising new strategy for the immunotherapy of HCC-SM.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123990"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964898","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2026.123991
Lipeng Qiao , Jueying Chen , Yongping Liang , Ying Huang , Meng Li , Yutong Yang , Baolin Guo
Diabetic wounds are a major complication for diabetic patients, with the high sugar and high ROS microenvironment leading to slow healing and a high risk of infection. To tackle these issues effectively, there is a critical need for advanced wound care solutions that can dynamically respond to the fluctuating conditions within the wound bed. In this study, we developed an intelligent, responsive hydrogel dressing designed to modulate the wound microenvironment to promote diabetic wound healing. This hydrogel is capable of responsively releasing the blood glucose-regulating drug (sitagliptin (Sit)) and, in accordance with the inflammatory condition, it dispenses the anti-inflammatory drug nimesulide (Nim) on demand. Consequently, it ameliorates the diabetic wound microenvironment, greatly accelerating wound healing. This hydrogel is composed of carboxymethyl chitosan (CMC), oxidized hyaluronic acid methacrylate (OHM), 1-butyl-3-vinylimidazolium bromide (IL), Sit, and methoxy poly(ethylene glycol)-thioketal-poly(ε-caprolactone)@Nim (GKL@Nim (GN)) micelles that release anti-inflammatory drugs in response to ROS, forming a Schiff base/double bond dual network intelligent hydrogel. The hydrogel demonstrates good performance in responsive drug release, in vitro inflammatory modulation, ionic conductivity, swelling, biodegradability, and self-healing capabilities. In the full-thickness skin defect wound healing assay using a Type 2 Diabetes Mellitus (T2DM) mouse model, the hydrogel group exhibited remarkable therapeutic effects, achieving an 80.2 % wound closure ratio on day 7, markedly superior to the Tegaderm™ film group (24.2 %). By day 14, wound closure in the hydrogel group reached 96.3 %. Histological assessments verified that hydrogel significantly enhanced angiogenesis and collagen deposition. Immunohistochemical analyses confirmed the hydrogel's efficacy in substantially decreasing IL-6 levels (25.7 %) and augmenting CD31 expression (315.3 %). Collectively, this intelligent hydrogel dressing holds immense promise for the treatment of diabetic wounds.
{"title":"Intelligent drug delivery-wound healing integrated hydrogel dressing for Type 2 Diabetes Mellitus wounds with wound microenvironment modulation","authors":"Lipeng Qiao , Jueying Chen , Yongping Liang , Ying Huang , Meng Li , Yutong Yang , Baolin Guo","doi":"10.1016/j.biomaterials.2026.123991","DOIUrl":"10.1016/j.biomaterials.2026.123991","url":null,"abstract":"<div><div>Diabetic wounds are a major complication for diabetic patients, with the high sugar and high ROS microenvironment leading to slow healing and a high risk of infection. To tackle these issues effectively, there is a critical need for advanced wound care solutions that can dynamically respond to the fluctuating conditions within the wound bed. In this study, we developed an intelligent, responsive hydrogel dressing designed to modulate the wound microenvironment to promote diabetic wound healing. This hydrogel is capable of responsively releasing the blood glucose-regulating drug (sitagliptin (Sit)) and, in accordance with the inflammatory condition, it dispenses the anti-inflammatory drug nimesulide (Nim) on demand. Consequently, it ameliorates the diabetic wound microenvironment, greatly accelerating wound healing. This hydrogel is composed of carboxymethyl chitosan (CMC), oxidized hyaluronic acid methacrylate (OHM), 1-butyl-3-vinylimidazolium bromide (IL), Sit, and methoxy poly(ethylene glycol)-thioketal-poly(ε-caprolactone)@Nim (GKL@Nim (GN)) micelles that release anti-inflammatory drugs in response to ROS, forming a Schiff base/double bond dual network intelligent hydrogel. The hydrogel demonstrates good performance in responsive drug release, <em>in vitro</em> inflammatory modulation, ionic conductivity, swelling, biodegradability, and self-healing capabilities. In the full-thickness skin defect wound healing assay using a Type 2 Diabetes Mellitus (T2DM) mouse model, the hydrogel group exhibited remarkable therapeutic effects, achieving an 80.2 % wound closure ratio on day 7, markedly superior to the Tegaderm™ film group (24.2 %). By day 14, wound closure in the hydrogel group reached 96.3 %. Histological assessments verified that hydrogel significantly enhanced angiogenesis and collagen deposition. Immunohistochemical analyses confirmed the hydrogel's efficacy in substantially decreasing IL-6 levels (25.7 %) and augmenting CD31 expression (315.3 %). Collectively, this intelligent hydrogel dressing holds immense promise for the treatment of diabetic wounds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123991"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922187","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2026.123987
Jinyan Hu , Yuqi Xiang , Zhenlin Zhang , Jinming Cai , Yang Wang , Hongjing Dou , Dengyu Pan , Longxiang Shen , Bijiang Geng
The design of biodegradable multimodal nanomedicines such as sonozymes is indispensable for clinical applications. It is thus required to develop NIR-fluorescence imaging technologies allowing for in-time monitoring of their metabolic dynamics in vivo for spatiotemporally precise treatments owing to their unpredictability in vivo degradation dynamics. To this end, a biodegradable Mn (III)-based sonozyme in the MnO2γ-phase was synthesized by atomic valence engineering (AVE) strategy based on hydrolysis and dismutation of Mn (III) ions. This synthetic strategy can tune the Mn (III) content from 70 % to 82 % and thus oxygen vacancy (VO) concentration at room temperature via charge compensation. As a result, VO-enhanced sonodynamic and nanozyme effects were observed. Moreover, NIR-fluorescent carbon dots (NIR-CDs) were in-situ assembled on the nanoflower surface by forming Mn (III)–N complexes, which quenched the fluorescence. In vitro and in vivo fluorescence imaging showed tumor-specific degradable dynamics owing to the biodegradation triggered by GSH overexpressed in the tumor microenvironment. Enhanced sonodynamic immunotherapy efficacy against both local and distant tumors was achieved by the synergism of VO-mediated sonodynamic enhancement, Mn (III)-mediated GSH depletion, hypoxia alleviation and STING activation. Our results revealed that the Mn (III)-regulated nanozyme system as a biodegradable “all in one” theranostic platform can facilitate spatiotemporally controlled NIR imaging guided multimodal treatments in combating metastatic cancers.
{"title":"Atomic-valence engineering of a Mn(III)-tuned sonozyme system for multimodal tumor immunotherapy","authors":"Jinyan Hu , Yuqi Xiang , Zhenlin Zhang , Jinming Cai , Yang Wang , Hongjing Dou , Dengyu Pan , Longxiang Shen , Bijiang Geng","doi":"10.1016/j.biomaterials.2026.123987","DOIUrl":"10.1016/j.biomaterials.2026.123987","url":null,"abstract":"<div><div>The design of biodegradable multimodal nanomedicines such as sonozymes is indispensable for clinical applications. It is thus required to develop NIR-fluorescence imaging technologies allowing for in-time monitoring of their metabolic dynamics <em>in vivo</em> for spatiotemporally precise treatments owing to their unpredictability <em>in vivo</em> degradation dynamics. To this end, a biodegradable Mn (III)-based sonozyme in the MnO<sub>2</sub> <em>γ</em>-phase was synthesized by atomic valence engineering (AVE) strategy based on hydrolysis and dismutation of Mn (III) ions. This synthetic strategy can tune the Mn (III) content from 70 % to 82 % and thus oxygen vacancy (<em>V</em><sub><em>O</em></sub>) concentration at room temperature via charge compensation. As a result, <em>V</em><sub><em>O</em></sub>-enhanced sonodynamic and nanozyme effects were observed. Moreover, NIR-fluorescent carbon dots (NIR-CDs) were in-situ assembled on the nanoflower surface by forming Mn (III)–N complexes, which quenched the fluorescence. <em>In vitro</em> and <em>in vivo</em> fluorescence imaging showed tumor-specific degradable dynamics owing to the biodegradation triggered by GSH overexpressed in the tumor microenvironment. Enhanced sonodynamic immunotherapy efficacy against both local and distant tumors was achieved by the synergism of <em>V</em><sub>O</sub>-mediated sonodynamic enhancement, Mn (III)-mediated GSH depletion, hypoxia alleviation and STING activation. Our results revealed that the Mn (III)-regulated nanozyme system as a biodegradable “all in one” theranostic platform can facilitate spatiotemporally controlled NIR imaging guided multimodal treatments in combating metastatic cancers.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123987"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922311","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 : 2026-01-05DOI: 10.1016/j.biomaterials.2025.123969
Yulin Sun , Lingling Jia , Jiachao Xiong , Yu'an Zhu , Hao Zhang , Feng Yang , Minjuan Wu , Hua Jiang , Yufei Li
Androgenetic alopecia (AGA), a prevalent non-scarring alopecia, poses significant therapeutic limitations due to the restricted efficacy and potential side effects of current interventions. Cell-derived nanovesicles (CNVs), noted for their biocompatibility and efficient delivery capacity, have been investigated as promising therapeutic carriers. Comparative studies of CNVs sourced from HaCat cells, adipose-derived stem cells, and dermal papilla cells demonstrated that those derived from dermal papilla cells exhibit enhanced cellular internalization and targeting specificity. Proteomic analyses revealed a notable suppression of Histone Deacetylase 1 (HDAC1) expression in balding scalp regions of AGA patients, suggesting involvement in cell cycle dysregulation and senescence-related processes. HDAC1-overexpressing nanovesicles were subsequently developed, characterized by high encapsulation efficiency, favorable biomimetic profiles, and cost-effective scalability. These engineered nanovesicles substantially improved cellular proliferation and migration capacities while mitigating dihydrotestosterone (DHT)-induced cytotoxicity. Transcriptomic evaluations suggested their role in promoting hair follicle regeneration via modulation of p53 and Wnt/β-Catenin signaling pathways. To address limitations in intradermal delivery, a dissolvable microneedle platform was constructed to enable precise, sustained release with excellent biocompatibility and targeted administration. Therapeutic efficacy was validated through comprehensive in vitro assays and in vivo models, supporting the translational potential of this cell-free nanotherapeutic strategy in AGA management.
{"title":"HDAC1-overexpressing dermal papilla cell-derived extracellular vesicles modulate p53 and Wnt/β-catenin signaling to rescue hair follicle regeneration in androgenetic alopecia","authors":"Yulin Sun , Lingling Jia , Jiachao Xiong , Yu'an Zhu , Hao Zhang , Feng Yang , Minjuan Wu , Hua Jiang , Yufei Li","doi":"10.1016/j.biomaterials.2025.123969","DOIUrl":"10.1016/j.biomaterials.2025.123969","url":null,"abstract":"<div><div>Androgenetic alopecia (AGA), a prevalent non-scarring alopecia, poses significant therapeutic limitations due to the restricted efficacy and potential side effects of current interventions. Cell-derived nanovesicles (CNVs), noted for their biocompatibility and efficient delivery capacity, have been investigated as promising therapeutic carriers. Comparative studies of CNVs sourced from HaCat cells, adipose-derived stem cells, and dermal papilla cells demonstrated that those derived from dermal papilla cells exhibit enhanced cellular internalization and targeting specificity. Proteomic analyses revealed a notable suppression of Histone Deacetylase 1 (HDAC1) expression in balding scalp regions of AGA patients, suggesting involvement in cell cycle dysregulation and senescence-related processes. HDAC1-overexpressing nanovesicles were subsequently developed, characterized by high encapsulation efficiency, favorable biomimetic profiles, and cost-effective scalability. These engineered nanovesicles substantially improved cellular proliferation and migration capacities while mitigating dihydrotestosterone (DHT)-induced cytotoxicity. Transcriptomic evaluations suggested their role in promoting hair follicle regeneration via modulation of p53 and Wnt/β-Catenin signaling pathways. To address limitations in intradermal delivery, a dissolvable microneedle platform was constructed to enable precise, sustained release with excellent biocompatibility and targeted administration. Therapeutic efficacy was validated through comprehensive in vitro assays and in vivo models, supporting the translational potential of this cell-free nanotherapeutic strategy in AGA management.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123969"},"PeriodicalIF":12.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922319","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 : 2026-01-04DOI: 10.1016/j.biomaterials.2026.123984
Qingquan Liu , Xinyue Yang , Xu Zhong , Wendong Liu , Jingjing Zhang , Siyuan Xiang , Mingqian Tan
Fucoidan, a marine-derived polysaccharide with versatile biological functions, holds strong potential for biomedical applications but is limited by low viscosity and poor gelling capacity. To address these challenges, we developed a bioengineered fucoidan-based hydrogel (Fuco-PGAB) by modulating intermolecular interactions with functionalized polyglutamic acid. This molecular design increased hydrogen-bonding density, yielding a hydrogel with robust rheological properties, including pronounced shear-thinning behavior and instantaneous self-healing. These features enable the material to dissipate peristaltic stress while protecting encapsulated bacteria during gastrointestinal transit. The Fuco-PGAB hydrogel enabled efficient oral delivery of both Gram-positive (Lactiplantibacillus plantarum 90) and Gram-negative (Escherichia coli Nissle 1917) probiotics. In simulated digestive fluids, probiotic survival increased by more than two orders of magnitude compared to free cells, and in vivo viability was sustained for up to 96 h. Beyond protection, the hydrogel alleviated oxidative stress in intestinal epithelial cells by maintaining glutathione redox balance, inhibiting lipid peroxidation, enhancing superoxide dismutase activity, and scavenging reactive oxygen species. In a mouse colitis model, probiotic-loaded Fuco-PGAB restored microbial composition by reducing pathogenic species, enriching beneficial taxa, and suppressing inflammation. By integrating the intrinsic properties of fucoidan with a tunable cross-linking strategy, this hydrogel prolongs intestinal retention, enhances probiotic colonization, and improves intervention impact. These findings establish Fuco-PGAB as a promising oral delivery platform for collaborative intervention in inflammatory bowel disease.
{"title":"Fucoidan-based hydrogel with ultrafast self-healing properties for enhanced probiotic delivery to alleviate colitis and microbiota dysbiosis in mice","authors":"Qingquan Liu , Xinyue Yang , Xu Zhong , Wendong Liu , Jingjing Zhang , Siyuan Xiang , Mingqian Tan","doi":"10.1016/j.biomaterials.2026.123984","DOIUrl":"10.1016/j.biomaterials.2026.123984","url":null,"abstract":"<div><div>Fucoidan, a marine-derived polysaccharide with versatile biological functions, holds strong potential for biomedical applications but is limited by low viscosity and poor gelling capacity. To address these challenges, we developed a bioengineered fucoidan-based hydrogel (Fuco-PGA<sub>B</sub>) by modulating intermolecular interactions with functionalized polyglutamic acid. This molecular design increased hydrogen-bonding density, yielding a hydrogel with robust rheological properties, including pronounced shear-thinning behavior and instantaneous self-healing. These features enable the material to dissipate peristaltic stress while protecting encapsulated bacteria during gastrointestinal transit. The Fuco-PGA<sub>B</sub> hydrogel enabled efficient oral delivery of both Gram-positive (<em>Lactiplantibacillus plantarum</em> 90) and Gram-negative (<em>Escherichia coli</em> Nissle 1917) probiotics. In simulated digestive fluids, probiotic survival increased by more than two orders of magnitude compared to free cells, and <em>in vivo</em> viability was sustained for up to 96 h. Beyond protection, the hydrogel alleviated oxidative stress in intestinal epithelial cells by maintaining glutathione redox balance, inhibiting lipid peroxidation, enhancing superoxide dismutase activity, and scavenging reactive oxygen species. In a mouse colitis model, probiotic-loaded Fuco-PGA<sub>B</sub> restored microbial composition by reducing pathogenic species, enriching beneficial taxa, and suppressing inflammation. By integrating the intrinsic properties of fucoidan with a tunable cross-linking strategy, this hydrogel prolongs intestinal retention, enhances probiotic colonization, and improves intervention impact. These findings establish Fuco-PGA<sub>B</sub> as a promising oral delivery platform for collaborative intervention in inflammatory bowel disease.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123984"},"PeriodicalIF":12.9,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922312","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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