Chemoimmunotherapy has emerged as a promising treatment modality for triple-negative breast cancer (TNBC). However, its clinical utility is often hindered by the severe toxicity of chemotherapeutic agents and the immunosuppressive nature of the tumor microenvironment (TME). Herein, we engineer an injectable 5-fluorouracil-constituted DNA hydrogel embedded with quercetin (Q-5FDHG) through a novel DNA amplification reaction to navigate these impediments in a dual-pronged manner. Q-5FDHG ensures progressive enzymatic degradation, which continuously releases 5-fluorouracil (5FU) and quercetin (Que). Que attenuates the secretion of C-C motif chemokine ligand 2 (CCL2), thereby reducing the recruitment of tumor-associated macrophages and remodeling the immunosuppressive TME. Simultaneously, 5FU inhibits tumor cell proliferation with reduced systemic toxicity by optimizing local administration and induces immunogenic cell death (ICD) to enhance tumor immunogenicity. In orthotopic murine models of TNBC, Q-5FDHG exhibits remarkably specific anti-tumor immune responses and boosts anti-tumor efficacy, resulting in significant inhibition of tumor growth and lung metastasis. This study demonstrates a unique chemoimmunotherapy efficacy induced by the chemotherapeutic agent 5FU and small-molecule compound Que from traditional Chinese medicine, and provides a safe and effective therapeutic strategy for TNBC with great promise for clinical translation.
{"title":"A 5-Fluorouracil-Constituted DNA Hydrogel Embedded with Quercetin Remodels Tumor Microenvironment for Robust Chemoimmunotherapy.","authors":"Yiping Li, Peipei Zhao, Junru Li, Yongming Han, Zhendong Gao, Xiaohan Cai, Siqi Tian, Wenzhi Yang, Chenyu Zhang, Shan Cao, Congshuo Chen, Siqiu Chen, Xianming Kong, Yabin Gong, Fengqin Li, Peifeng Liu","doi":"10.1002/adhm.202503744","DOIUrl":"https://doi.org/10.1002/adhm.202503744","url":null,"abstract":"<p><p>Chemoimmunotherapy has emerged as a promising treatment modality for triple-negative breast cancer (TNBC). However, its clinical utility is often hindered by the severe toxicity of chemotherapeutic agents and the immunosuppressive nature of the tumor microenvironment (TME). Herein, we engineer an injectable 5-fluorouracil-constituted DNA hydrogel embedded with quercetin (Q-5FDHG) through a novel DNA amplification reaction to navigate these impediments in a dual-pronged manner. Q-5FDHG ensures progressive enzymatic degradation, which continuously releases 5-fluorouracil (5FU) and quercetin (Que). Que attenuates the secretion of C-C motif chemokine ligand 2 (CCL2), thereby reducing the recruitment of tumor-associated macrophages and remodeling the immunosuppressive TME. Simultaneously, 5FU inhibits tumor cell proliferation with reduced systemic toxicity by optimizing local administration and induces immunogenic cell death (ICD) to enhance tumor immunogenicity. In orthotopic murine models of TNBC, Q-5FDHG exhibits remarkably specific anti-tumor immune responses and boosts anti-tumor efficacy, resulting in significant inhibition of tumor growth and lung metastasis. This study demonstrates a unique chemoimmunotherapy efficacy induced by the chemotherapeutic agent 5FU and small-molecule compound Que from traditional Chinese medicine, and provides a safe and effective therapeutic strategy for TNBC with great promise for clinical translation.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03744"},"PeriodicalIF":9.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pressure-sensitive adhesives (PSAs) are core materials for wound care and medical fixation, yet their clinical application is constrained by three key contradictions: high adhesiveness easily causes skin damage during peeling, while low adhesiveness leads to dressing edge lifting and increased infection risk, and traditional PSAs generally lack antibacterial and wound-healing-promoting functions. To address these issues, this study proposes a "function-integrated PSAs" strategy by combining emulsion-polymerized cationic polyacrylate (CPPSA) with tunable adhesion and antibacterial properties and chitosan (CS) for hemostasis and wound regulation. This CPPSA-CS system integrates three core synergistic functions: electrostatically targeting and disrupting bacterial cell membranes for antibacterial protection, optimizing adhesive performance to balance bonding stability and low-damage peeling, and accelerating hemostasis and mitigating inflammatory responses at the wound site to modulate the wound microenvironment. This study overcomes traditional PSAs' limitation of single fixation function through material and functional innovation, providing a new technical approach for multi-dimensional infected wound management with significant clinical translation value.
{"title":"Construction of Function-Integrated Pressure-Sensitive Adhesives for Their Application in Infected Wound Management.","authors":"Ketao Yan, Yuzhu Long, Hongmei Deng, Ziwei Xiang, Jiaqi Ao, Wei Wen, Shengfu Wang, Xiuhua Zhang, Qichao Zou, Huayu Xiong","doi":"10.1002/adhm.202505339","DOIUrl":"https://doi.org/10.1002/adhm.202505339","url":null,"abstract":"<p><p>Pressure-sensitive adhesives (PSAs) are core materials for wound care and medical fixation, yet their clinical application is constrained by three key contradictions: high adhesiveness easily causes skin damage during peeling, while low adhesiveness leads to dressing edge lifting and increased infection risk, and traditional PSAs generally lack antibacterial and wound-healing-promoting functions. To address these issues, this study proposes a \"function-integrated PSAs\" strategy by combining emulsion-polymerized cationic polyacrylate (CPPSA) with tunable adhesion and antibacterial properties and chitosan (CS) for hemostasis and wound regulation. This CPPSA-CS system integrates three core synergistic functions: electrostatically targeting and disrupting bacterial cell membranes for antibacterial protection, optimizing adhesive performance to balance bonding stability and low-damage peeling, and accelerating hemostasis and mitigating inflammatory responses at the wound site to modulate the wound microenvironment. This study overcomes traditional PSAs' limitation of single fixation function through material and functional innovation, providing a new technical approach for multi-dimensional infected wound management with significant clinical translation value.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05339"},"PeriodicalIF":9.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xueqin Wang, Hong Chen, Chuan Liu, Mengna Wan, Shangyi Zhao, Na Li, Shaofeng Duan, Shaobo Duan
Diabetic wound infection remains a devastating threat to human health, largely due to bacterial colonization and increased antibiotic resistance during conventional treatments, and alternative therapeutic strategies are thus urgent to improve diabetic wound healing. Herein, we developed a multifaceted nanoplatform (CuO@SiO2@NO@Au, CSNA NPs) consisting of a cupric oxide (CuO) core, a mesoporous silicon nanoshell loaded with nitric oxide (NO), and in situ grown ultrasmall Au nanoparticles (NPs) for improved diabetic wound treatment. The results showed that the prepared CSNA NPs exhibited remarkable dual-enzyme mimic activity of glucose oxidase (GOx) and peroxidase (POD), effectively oxidizing glucose to generate gluconic acid, thereby reducing the glucose levels and reversing the acidic wound microenvironment. In addition, the fabricated nanoplatform generated abundant H2O2, which was converted into highly toxic hydroxyl radical (·OH), leading to efficient bacterial eradication that was subsequently. Under near-infrared (NIR) light irradiation, the CSNA nanozyme also triggered the release of NO gas and aided in the removal of bacterial biofilms, collectively improving the wound microenvironment. By integrating chemodynamic therapy (CDT), photothermal therapy, and NO gas therapy, this self-activatable NIR- augmented nanozyme provides a promising antimicrobial strategy for diabetic wound treatment.
{"title":"An All-in-One Nanozyme for Synergistic Diabetic Wound Therapy: NIR-Augmented NO Release and Microenvironment Modulation.","authors":"Xueqin Wang, Hong Chen, Chuan Liu, Mengna Wan, Shangyi Zhao, Na Li, Shaofeng Duan, Shaobo Duan","doi":"10.1002/adhm.202505240","DOIUrl":"https://doi.org/10.1002/adhm.202505240","url":null,"abstract":"<p><p>Diabetic wound infection remains a devastating threat to human health, largely due to bacterial colonization and increased antibiotic resistance during conventional treatments, and alternative therapeutic strategies are thus urgent to improve diabetic wound healing. Herein, we developed a multifaceted nanoplatform (CuO@SiO<sub>2</sub>@NO@Au, CSNA NPs) consisting of a cupric oxide (CuO) core, a mesoporous silicon nanoshell loaded with nitric oxide (NO), and in situ grown ultrasmall Au nanoparticles (NPs) for improved diabetic wound treatment. The results showed that the prepared CSNA NPs exhibited remarkable dual-enzyme mimic activity of glucose oxidase (GOx) and peroxidase (POD), effectively oxidizing glucose to generate gluconic acid, thereby reducing the glucose levels and reversing the acidic wound microenvironment. In addition, the fabricated nanoplatform generated abundant H<sub>2</sub>O<sub>2</sub>, which was converted into highly toxic hydroxyl radical (·OH), leading to efficient bacterial eradication that was subsequently. Under near-infrared (NIR) light irradiation, the CSNA nanozyme also triggered the release of NO gas and aided in the removal of bacterial biofilms, collectively improving the wound microenvironment. By integrating chemodynamic therapy (CDT), photothermal therapy, and NO gas therapy, this self-activatable NIR- augmented nanozyme provides a promising antimicrobial strategy for diabetic wound treatment.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05240"},"PeriodicalIF":9.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingming Gao, Kang Zhu, Zhao Wang, Xiaoyin Li, Liping Fang, Liwei Chen, Hongyu Mou, Xing Gao, Jing Feng, Jibin Song
Hafnium oxide (HfO2)-based nanomaterials are emerging as powerful tools to enhance radiotherapy by utilizing their high atomic number (Z). By depositing a greater radiation dose directly within tumors, they offer a promising route to improve treatment efficacy. This review traces the development of HfO2 nanoradiosensitizers, starting with the clinically established NBTXR3, an approved hafnium-based benchmark for several solid tumors. We analyze the structural characteristics and radiosensitization mechanisms of nanoscale HfO2, which include improved X-ray absorption, radical generation, and immunomodulation. Key synthesis methods such as sol-gel, precipitation, and hydrothermal approaches are evaluated in detail, with emphasis on their tunable parameters and reproducibility. Recent progress focuses on material optimization through size control, surface engineering, composite design, and Hf-MOFs, as well as combination strategies. Despite encouraging preclinical results, challenges remain in scalable fabrication, long-term biosafety, and clinical translation. Future directions point toward smart stimuli-responsive platforms and multimodal theranostic systems. This review highlights the potential of HfO2 to precision radiotherapy while acknowledging existing translational challenges.
{"title":"Engineering Hafnium Oxide-Based Nanoplatforms for Precision Radiosensitization.","authors":"Mingming Gao, Kang Zhu, Zhao Wang, Xiaoyin Li, Liping Fang, Liwei Chen, Hongyu Mou, Xing Gao, Jing Feng, Jibin Song","doi":"10.1002/adhm.202505200","DOIUrl":"https://doi.org/10.1002/adhm.202505200","url":null,"abstract":"<p><p>Hafnium oxide (HfO<sub>2</sub>)-based nanomaterials are emerging as powerful tools to enhance radiotherapy by utilizing their high atomic number (Z). By depositing a greater radiation dose directly within tumors, they offer a promising route to improve treatment efficacy. This review traces the development of HfO<sub>2</sub> nanoradiosensitizers, starting with the clinically established NBTXR3, an approved hafnium-based benchmark for several solid tumors. We analyze the structural characteristics and radiosensitization mechanisms of nanoscale HfO<sub>2</sub>, which include improved X-ray absorption, radical generation, and immunomodulation. Key synthesis methods such as sol-gel, precipitation, and hydrothermal approaches are evaluated in detail, with emphasis on their tunable parameters and reproducibility. Recent progress focuses on material optimization through size control, surface engineering, composite design, and Hf-MOFs, as well as combination strategies. Despite encouraging preclinical results, challenges remain in scalable fabrication, long-term biosafety, and clinical translation. Future directions point toward smart stimuli-responsive platforms and multimodal theranostic systems. This review highlights the potential of HfO<sub>2</sub> to precision radiotherapy while acknowledging existing translational challenges.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05200"},"PeriodicalIF":9.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xueqi Liang, Zhen Liu, Nan Wang, Xiao-Kun Ouyang, Junhong Ling
Immunogenic cell death (ICD) induced by calcium overload holds great promise for reversing the immunosuppressive tumor microenvironment (TME) and improving cancer immunotherapy. However, achieving sustained calcium dysregulation remains a major challenge. Herein, we report a novel nanoplatform, termed Ca@CMPN, which co-delivers calcium hydride and curcumin using a mesoporous polydopamine carrier for synergistic ion-interference and gas immunotherapy. Upon encountering the acidic TME, Ca@CMPN disintegrates to release Ca2+, initiating intracellular calcium overload, and concurrently generates hydrogen gas (H2). Crucially, the co-released curcumin acts from within the cell, amplifying the calcium overload by disrupting organellar calcium homeostasis, thereby ensuring robust ICD. Meanwhile, H2 serves as a potent immunoadjuvant to alleviate oxidative stress and remodel the immunosuppressive TME. Both in vitro and in vivo studies demonstrate that Ca@CMPN effectively inhibits tumor growth and reprograms the TME, as evidenced by enhanced dendritic cell maturation, activation of cytotoxic T cells, and elevated levels of pro-inflammatory cytokines (interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α)). This work presents a paradigm-shifting strategy that synergizes ion-interference therapy with hydrogen immunotherapy, offering a powerful nanoplatform to unlock the full potential of cancer immunotherapy.
{"title":"Synergistic Calcium Overload and Hydrogen Release Potentiate Robust Antitumor Immunity.","authors":"Xueqi Liang, Zhen Liu, Nan Wang, Xiao-Kun Ouyang, Junhong Ling","doi":"10.1002/adhm.202505332","DOIUrl":"https://doi.org/10.1002/adhm.202505332","url":null,"abstract":"<p><p>Immunogenic cell death (ICD) induced by calcium overload holds great promise for reversing the immunosuppressive tumor microenvironment (TME) and improving cancer immunotherapy. However, achieving sustained calcium dysregulation remains a major challenge. Herein, we report a novel nanoplatform, termed Ca@CMPN, which co-delivers calcium hydride and curcumin using a mesoporous polydopamine carrier for synergistic ion-interference and gas immunotherapy. Upon encountering the acidic TME, Ca@CMPN disintegrates to release Ca<sup>2+</sup>, initiating intracellular calcium overload, and concurrently generates hydrogen gas (H<sub>2</sub>). Crucially, the co-released curcumin acts from within the cell, amplifying the calcium overload by disrupting organellar calcium homeostasis, thereby ensuring robust ICD. Meanwhile, H<sub>2</sub> serves as a potent immunoadjuvant to alleviate oxidative stress and remodel the immunosuppressive TME. Both in vitro and in vivo studies demonstrate that Ca@CMPN effectively inhibits tumor growth and reprograms the TME, as evidenced by enhanced dendritic cell maturation, activation of cytotoxic T cells, and elevated levels of pro-inflammatory cytokines (interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α)). This work presents a paradigm-shifting strategy that synergizes ion-interference therapy with hydrogen immunotherapy, offering a powerful nanoplatform to unlock the full potential of cancer immunotherapy.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05332"},"PeriodicalIF":9.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The gut epithelium ensures nutrient absorption and barrier protection, functions tightly linked to its 3D architecture and dynamic mechanical activity. To dissect how mechanical forces influence intestinal physiology, we developed a stretchable 3D colon-on-chip that integrates tunable topography, stiffness and peristalsis-like motion within a physiologically relevant microenvironment. The model employs 3D scaffolds composed of either pure collagen I or mechanically reinforced interpenetrated network (IPN) made of collagen I and PEGDA. Tensile tests mimicking peristalsis revealed that both hydrogels soften upon stretching, with the IPN maintaining higher stiffness than pure collagen. Using this platform, we applied cyclic stretching for 24 to 72 h to co-cultures of stromal and epithelial cells, and systematically assessed the contributions of stiffness, curvature and shear stress. We found that the stretching was a dominant factor governing epithelial behavior, markedly enhancing proliferation and apicobasal polarization without altering differentiation. Altogether, this work introduces a next-generation colon-on-chip that unites mechanical control and biological complexity, providing a powerful tool to unravel how physical cues orchestrate intestinal homeostasis and paving the way for modeling disease states such as colorectal cancer and inflammation.
{"title":"A New 3D Colon on a Chip to Decipher the Influence of Mechanical Forces on the Physiological Cellular Ecosystem.","authors":"Moencopi Bernheim-Dennery, Lauriane Gérémie, Julie Brun, Lucas Chassatte, Giacomo Gropplero, Réda Bouras, Jieun Choo, Bertrand Cinquin, Alba Marcellan, Danijela Matic Vignjevic, Stéphanie Descroix","doi":"10.1002/adhm.202505483","DOIUrl":"https://doi.org/10.1002/adhm.202505483","url":null,"abstract":"<p><p>The gut epithelium ensures nutrient absorption and barrier protection, functions tightly linked to its 3D architecture and dynamic mechanical activity. To dissect how mechanical forces influence intestinal physiology, we developed a stretchable 3D colon-on-chip that integrates tunable topography, stiffness and peristalsis-like motion within a physiologically relevant microenvironment. The model employs 3D scaffolds composed of either pure collagen I or mechanically reinforced interpenetrated network (IPN) made of collagen I and PEGDA. Tensile tests mimicking peristalsis revealed that both hydrogels soften upon stretching, with the IPN maintaining higher stiffness than pure collagen. Using this platform, we applied cyclic stretching for 24 to 72 h to co-cultures of stromal and epithelial cells, and systematically assessed the contributions of stiffness, curvature and shear stress. We found that the stretching was a dominant factor governing epithelial behavior, markedly enhancing proliferation and apicobasal polarization without altering differentiation. Altogether, this work introduces a next-generation colon-on-chip that unites mechanical control and biological complexity, providing a powerful tool to unravel how physical cues orchestrate intestinal homeostasis and paving the way for modeling disease states such as colorectal cancer and inflammation.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05483"},"PeriodicalIF":9.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dong Joon Lee, Vinayak Juvekar, Yu Cao, Jong Kyu Baek, Jong Beom Kang, Min Cheol Park, Sauraj, Abijith Karyapallathil Sadashivan, Myoung Ki Cho, Gil Ho Lee, Tae Jun Park, Hyuk Kang, Sung Jae Shin, Zhihong Liu, Hwan Myung Kim
Two-photon excitation (TPE) phototherapy provides high spatial resolution and deep-tissue penetration with minimal invasiveness. In this study, we introduce a modular and scalable approach to transform a traditional TPE imaging dye into a highly effective type-I photosensitizer (PS) through minimal chemical modification. The newly developed selenium-bridged dye demonstrates pronounced two-photon absorption, efficient ROS generation upon TPE, and strong antitumor activity both in vitro and in hypoxic in vivo tumor environments. For subcellular targeting, we conjugated organelle-specific functional groups to produce a series of derivatives, thereby achieving accurate ROS localization and improved PDT efficacy. Leveraging the amphiphilic properties of these PSs, we established a self-assembled dye-combination micelle (DCM) approach that enables the co-assembly of membrane- and mitochondria-targeted derivatives into stable, carrier-free nanoparticles. This multi-dye strategy facilitates enhanced phototoxicity by simultaneously impairing multiple organelle functions. Additional surface modification using the RGD (Arg-Gly-Asp) peptide sequence imparts tumor selectivity through αvβ3 integrin-mediated uptake, yielding DCM nanoparticles that selectively induce phototoxic effects in cancer cells while sparing healthy tissue. Importantly, this platform demonstrates spatially restricted, two-photon-triggered therapeutic efficacy in freshly excised human colon tumor tissue, emphasizing its potential for clinical translation.
{"title":"Dye-Combination Micelles for Two-Photon Phototherapy.","authors":"Dong Joon Lee, Vinayak Juvekar, Yu Cao, Jong Kyu Baek, Jong Beom Kang, Min Cheol Park, Sauraj, Abijith Karyapallathil Sadashivan, Myoung Ki Cho, Gil Ho Lee, Tae Jun Park, Hyuk Kang, Sung Jae Shin, Zhihong Liu, Hwan Myung Kim","doi":"10.1002/adhm.202505557","DOIUrl":"https://doi.org/10.1002/adhm.202505557","url":null,"abstract":"<p><p>Two-photon excitation (TPE) phototherapy provides high spatial resolution and deep-tissue penetration with minimal invasiveness. In this study, we introduce a modular and scalable approach to transform a traditional TPE imaging dye into a highly effective type-I photosensitizer (PS) through minimal chemical modification. The newly developed selenium-bridged dye demonstrates pronounced two-photon absorption, efficient ROS generation upon TPE, and strong antitumor activity both in vitro and in hypoxic in vivo tumor environments. For subcellular targeting, we conjugated organelle-specific functional groups to produce a series of derivatives, thereby achieving accurate ROS localization and improved PDT efficacy. Leveraging the amphiphilic properties of these PSs, we established a self-assembled dye-combination micelle (DCM) approach that enables the co-assembly of membrane- and mitochondria-targeted derivatives into stable, carrier-free nanoparticles. This multi-dye strategy facilitates enhanced phototoxicity by simultaneously impairing multiple organelle functions. Additional surface modification using the RGD (Arg-Gly-Asp) peptide sequence imparts tumor selectivity through α<sub>v</sub>β<sub>3</sub> integrin-mediated uptake, yielding DCM nanoparticles that selectively induce phototoxic effects in cancer cells while sparing healthy tissue. Importantly, this platform demonstrates spatially restricted, two-photon-triggered therapeutic efficacy in freshly excised human colon tumor tissue, emphasizing its potential for clinical translation.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05557"},"PeriodicalIF":9.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziyan Liu, Xuetong Wang, Ziyang Liu, Jing Jiang, Xiao Lin, Zhe Xiao, Ping Zhang, Huan Zhou, Lei Yang
Precise control of reactive oxygen species (ROS) is indispensable during tissue repairing. Inorganic nanozymes such as cerium dioxide (CeO2) have emerged as potent ROS modulators, however, their fixed catalytic activity prevents on-demand adaptation to the rapidly changing immune microenvironment. Here, we reported a magnetically responsive dynamic antioxidant system that autonomously tunes its ROS-scavenging capacity on demand. Selenium (Se) doping was first exploited to engineer high-density oxygen vacancies (Vo) in the CeO2 lattice, enabling the nanozyme intrinsic antioxidant activity enhancement. Its catalytic efficiency could be further amplified under a static magnetic field (SMF). In vitro analysis revealed that Se-CeO2 under SMF significantly promoted the polarization of macrophages toward the pro-regenerative M2 phenotype. The as-prepared Se-CeO2 was subsequently loaded into a sodium alginate-hyaluronic acid hydrogel (SCSH-Gel), witnessed to protect chondrocytes and fibroblasts from oxidative stress in vitro. Followed in vivo tests found SMF and Se-CeO2 synergistically accelerate neocartilage formation in a cartilage defect model and promoted re-epithelialization in a full-thickness skin-wound model. Collectively, our results demonstrated that Se doping coupled with magnetic actuation enables inorganic nanozymes to dynamically modulate ROS homeostasis, offering a versatile strategy for precisely programming the microenvironment to facilitate tissue regeneration.
{"title":"A Magnetically Responsive Selenium-Doped CeO<sub>2</sub> Nanozyme for On-Demand Reactive Oxygen Species Modulation and Enhanced Tissue Regeneration.","authors":"Ziyan Liu, Xuetong Wang, Ziyang Liu, Jing Jiang, Xiao Lin, Zhe Xiao, Ping Zhang, Huan Zhou, Lei Yang","doi":"10.1002/adhm.202505174","DOIUrl":"https://doi.org/10.1002/adhm.202505174","url":null,"abstract":"<p><p>Precise control of reactive oxygen species (ROS) is indispensable during tissue repairing. Inorganic nanozymes such as cerium dioxide (CeO<sub>2</sub>) have emerged as potent ROS modulators, however, their fixed catalytic activity prevents on-demand adaptation to the rapidly changing immune microenvironment. Here, we reported a magnetically responsive dynamic antioxidant system that autonomously tunes its ROS-scavenging capacity on demand. Selenium (Se) doping was first exploited to engineer high-density oxygen vacancies (Vo) in the CeO<sub>2</sub> lattice, enabling the nanozyme intrinsic antioxidant activity enhancement. Its catalytic efficiency could be further amplified under a static magnetic field (SMF). In vitro analysis revealed that Se-CeO<sub>2</sub> under SMF significantly promoted the polarization of macrophages toward the pro-regenerative M2 phenotype. The as-prepared Se-CeO<sub>2</sub> was subsequently loaded into a sodium alginate-hyaluronic acid hydrogel (SCSH-Gel), witnessed to protect chondrocytes and fibroblasts from oxidative stress in vitro. Followed in vivo tests found SMF and Se-CeO<sub>2</sub> synergistically accelerate neocartilage formation in a cartilage defect model and promoted re-epithelialization in a full-thickness skin-wound model. Collectively, our results demonstrated that Se doping coupled with magnetic actuation enables inorganic nanozymes to dynamically modulate ROS homeostasis, offering a versatile strategy for precisely programming the microenvironment to facilitate tissue regeneration.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05174"},"PeriodicalIF":9.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai Feng, Jiajia An, Xinmiao Zhang, Gaoling Li, Yiling Ruan, Hongxiang Huang, Yanlei Sun, Xuan Liu, Xiaolian Sun
Myocardial infarction (MI) is a worldwide disease with high prevalence and mortality, but it still lacks efficient therapeutic strategies. Since it has been found that numerous cell types are involved in the pathological changes of MI, including fibroblasts, cardiomyocytes, immune cells, and endothelial cells, targeting a cell type seems no longer the ideal treatment. Here, we developed a ROS-responsive delivery system for microRNA-21 (miR-21) and DB1976 (a PU.1 inhibitor) to remodel the cardiac environment in a relatively comprehensive way. MiR-21 exhibited cardioprotective effects by improving angiogenesis, reducing apoptosis, and combating inflammation. However, the accompanying fibrosis impedes its therapeutic effect. DB1976, as a PU.1 inhibitor, could effectively inhibit fibrosis and alleviate the adverse effects of miR-21. In a mouse MI model, the hydrogel (termed mesoporous silica nanoparticles (MSN)/miR-21-DB hydrogel) significantly improved cardiac function through remodeling cardiomyocytes, macrophages, fibroblasts, and vascular endothelial cells. This work provides a new approach for repairing damaged cardiac tissue by simultaneously regulating multiple cell types in the cardiac microenvironment.
{"title":"One Stone, Four Birds: Multiple Modulation of Infarct Microenvironment-Based ROS-Responsive Hydrogel for Cardiac Repair.","authors":"Kai Feng, Jiajia An, Xinmiao Zhang, Gaoling Li, Yiling Ruan, Hongxiang Huang, Yanlei Sun, Xuan Liu, Xiaolian Sun","doi":"10.1002/adhm.202505502","DOIUrl":"https://doi.org/10.1002/adhm.202505502","url":null,"abstract":"<p><p>Myocardial infarction (MI) is a worldwide disease with high prevalence and mortality, but it still lacks efficient therapeutic strategies. Since it has been found that numerous cell types are involved in the pathological changes of MI, including fibroblasts, cardiomyocytes, immune cells, and endothelial cells, targeting a cell type seems no longer the ideal treatment. Here, we developed a ROS-responsive delivery system for microRNA-21 (miR-21) and DB1976 (a PU.1 inhibitor) to remodel the cardiac environment in a relatively comprehensive way. MiR-21 exhibited cardioprotective effects by improving angiogenesis, reducing apoptosis, and combating inflammation. However, the accompanying fibrosis impedes its therapeutic effect. DB1976, as a PU.1 inhibitor, could effectively inhibit fibrosis and alleviate the adverse effects of miR-21. In a mouse MI model, the hydrogel (termed mesoporous silica nanoparticles (MSN)/miR-21-DB hydrogel) significantly improved cardiac function through remodeling cardiomyocytes, macrophages, fibroblasts, and vascular endothelial cells. This work provides a new approach for repairing damaged cardiac tissue by simultaneously regulating multiple cell types in the cardiac microenvironment.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e05502"},"PeriodicalIF":9.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Uveitis is a prevalent ocular inflammatory condition and a major contributor to global vision impairment. The inflammatory cascade activates the complement system, resulting in the production of C5a, which interacts with its receptor C5aR1 on microglia, promoting excessive neutrophil recruitment and reactive oxygen species (ROS) bursts. In this study, we develop a targeted drug delivery system by conjugating small extracellular vesicles with the microglia-binding peptide MG1 using Sortase A. The C5aR1 antagonist Avacopan was loaded into the modified EVs via extrusion. Using a lipopolysaccharide (LPS)-induced endotoxin-induced uveitis (EIU) model, we evaluate the effects of MG1-EVs/Ava on ocular inflammatory pathology, microglial migration, and retinal cytokine expression. In vitro assays are performed to assess the cytotoxicity of Avacopan as well as its impact on ROS generation and pro-inflammatory cytokine production. In addition, data-independent acquisition (DIA) proteomics analysis is conducted to explore the downstream signaling pathways involved in MG1-EVs/Ava-mediated therapeutic effects. In rescue experiments, siRNA-mediated knockdown of MAPK9 reverses the downregulation of C5aR1 and pro-inflammatory cytokines, further supporting its role in mediating the therapeutic effects of MG1-EVs/Ava. The findings of this study demonstrate both the therapeutic efficacy and mechanistic basis of MG1-EVs/Ava, highlighting its potential as a promising treatment strategy for infectious uveitis.
{"title":"Targeted Delivery of Avacopan via Sortase A-Modified Extracellular Vesicles Attenuates Endotoxin-Induced Retinal Inflammation.","authors":"Dexin Meng, Yidan Chen, Cong Cui, Mingxuan Huang, Jiajing Zhu, Haomin Lu, Hao Zhang, Dawei Sun","doi":"10.1002/adhm.202504723","DOIUrl":"https://doi.org/10.1002/adhm.202504723","url":null,"abstract":"<p><p>Uveitis is a prevalent ocular inflammatory condition and a major contributor to global vision impairment. The inflammatory cascade activates the complement system, resulting in the production of C5a, which interacts with its receptor C5aR1 on microglia, promoting excessive neutrophil recruitment and reactive oxygen species (ROS) bursts. In this study, we develop a targeted drug delivery system by conjugating small extracellular vesicles with the microglia-binding peptide MG1 using Sortase A. The C5aR1 antagonist Avacopan was loaded into the modified EVs via extrusion. Using a lipopolysaccharide (LPS)-induced endotoxin-induced uveitis (EIU) model, we evaluate the effects of MG1-EVs/Ava on ocular inflammatory pathology, microglial migration, and retinal cytokine expression. In vitro assays are performed to assess the cytotoxicity of Avacopan as well as its impact on ROS generation and pro-inflammatory cytokine production. In addition, data-independent acquisition (DIA) proteomics analysis is conducted to explore the downstream signaling pathways involved in MG1-EVs/Ava-mediated therapeutic effects. In rescue experiments, siRNA-mediated knockdown of MAPK9 reverses the downregulation of C5aR1 and pro-inflammatory cytokines, further supporting its role in mediating the therapeutic effects of MG1-EVs/Ava. The findings of this study demonstrate both the therapeutic efficacy and mechanistic basis of MG1-EVs/Ava, highlighting its potential as a promising treatment strategy for infectious uveitis.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e04723"},"PeriodicalIF":9.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}