Advanced Healthcare Materials最新文献_第7页

Engineered Microvascular Model of the Blood–Brain–Tumor Barrier Reveals Endothelial Remodeling in Diffuse Midline Glioma (Adv. Healthcare Mater. 37/2026) 血-脑-瘤屏障工程微血管模型揭示弥漫性中线胶质瘤内皮重塑（Adv. Healthcare Mater. 37/2026）

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 DOI: 10.1002/adhm.71677

Kimberly R. Bennett, Yann S. Vanrobaeys, Tessy Teboh, Zakiya Smith, Anderson Scott, Cynthia Hajal, Paula T. Hammond, Joelle P. Straehla

引用次数: 0

Protein-Polymer Dynamic Hydrogels Utilizing Native Ligand Binding for Injectable Therapeutic Delivery and 3D Printing. 利用天然配体结合的蛋白质-聚合物动态水凝胶用于注射治疗递送和3D打印。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 DOI: 10.1002/adhm.71810

S Cem Millik, Yonghui Wang, Kefan Song, Jessica M Snyder, LeAnn Le, Lauren G Brown, Shanny Hsuan Kuo, Ashleigh B Theberge, Suzie H Pun, Alshakim Nelson

{"title":"Protein-Polymer Dynamic Hydrogels Utilizing Native Ligand Binding for Injectable Therapeutic Delivery and 3D Printing.","authors":"S Cem Millik, Yonghui Wang, Kefan Song, Jessica M Snyder, LeAnn Le, Lauren G Brown, Shanny Hsuan Kuo, Ashleigh B Theberge, Suzie H Pun, Alshakim Nelson","doi":"10.1002/adhm.71810","DOIUrl":"https://doi.org/10.1002/adhm.71810","url":null,"abstract":"<p><p>Dynamic hydrogels comprising networks formed from reversible interactions have shown utility in minimally invasive delivery of encapsulated therapeutics, as well as in extrusion-based 3D printing of tissue-mimetic structures. Here, we report dynamic nanocolloidal hydrogels formed from the co-assembly of spheroidal hyperbranched poly(glycerol) (HPG) and soluble albumin nanoparticles (SANs). Functionalization of the HPG with palmitate (a natural ligand of serum albumin) appears to enable self-association of the HPG, as well as its interaction with SANs, to form dynamic networks. The properties of these networks can be tuned by modifying the size of the SAN in addition to other formulation parameters. To highlight the utility of these dynamic hydrogels, we demonstrate (i) in vitro and in vivo release of a model protein therapeutic from these injectable materials, (ii) preliminarily evaluate biocompatibility of these materials in a murine model, and (iii) demonstrate extrusion-based 3D printing using these materials.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71810"},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134303","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}

引用次数: 0

Selective Blood Cell Hitchhiking in Whole Blood With Ionic Liquid-Coated PLGA Nanoparticles to Redirect Biodistribution After Intravenous Injection (Adv. Healthcare Mater. 37/2026) 离子液体包被的PLGA纳米颗粒在全血中选择性搭车以改变静脉注射后的生物分布（Adv. Healthcare Mater. 37/2026）

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 DOI: 10.1002/adhm.71674

Christine M. Hamadani, Duoyi Hu, Gaya S. Dasanayake, Tanveer Shaikh, Gagandeep Singh, Claylee M. Chism, Priyavrat Vashisth, Meghan Gorniak, Wake G. Monroe, George Taylor, Anya Merrell, Emilia Huff, Amber Cecil, Danny Ly, Camille Sperier, Jordan Gill, Mercedes C. Pride, Rebekah Heintz, Karen Wong, Mehjabeen Hossain, Deauntaye Jones, Joy Dhar, Alison Banka, Sara X. Edgecomb, Joh'nis Randall, Donovan S. Darlington, Jaylon Everett, Ethan Jarrett, Thomas A. Werfel, Nicholas C. Fitzkee, Omolola Eniola-Adefeso, Eden E. L. Tanner

{"title":"Selective Blood Cell Hitchhiking in Whole Blood With Ionic Liquid-Coated PLGA Nanoparticles to Redirect Biodistribution After Intravenous Injection (Adv. Healthcare Mater. 37/2026)","authors":"Christine M. Hamadani, Duoyi Hu, Gaya S. Dasanayake, Tanveer Shaikh, Gagandeep Singh, Claylee M. Chism, Priyavrat Vashisth, Meghan Gorniak, Wake G. Monroe, George Taylor, Anya Merrell, Emilia Huff, Amber Cecil, Danny Ly, Camille Sperier, Jordan Gill, Mercedes C. Pride, Rebekah Heintz, Karen Wong, Mehjabeen Hossain, Deauntaye Jones, Joy Dhar, Alison Banka, Sara X. Edgecomb, Joh'nis Randall, Donovan S. Darlington, Jaylon Everett, Ethan Jarrett, Thomas A. Werfel, Nicholas C. Fitzkee, Omolola Eniola-Adefeso, Eden E. L. Tanner","doi":"10.1002/adhm.71674","DOIUrl":"https://doi.org/10.1002/adhm.71674","url":null,"abstract":"<p><b>Blood-Ionic Liquid Nanoparticle Interactions</b></p><p>Ionic liquid-coated nanoparticles navigate the bloodstream by hitchhiking on endogenous blood cells, redirecting circulation toward target tissues. By tuning ionic liquid chemistry, nanoparticles selectively associate with red blood cells, platelets, and immune cells, opening new routes for intravenous drug delivery to therapeutically challenging organs, including the central nervous system. More details can be found in the Research Article by Eden E. L. Tanner and co-workers (DOI: 10.1002/adhm.71494).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.71674","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149125721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Patient-Derived 3D Heart-On-a-Chip Model of Dilated Cardiomyopathy With Embedded Bead-Based Mapping of Tissue Contractility 基于嵌入的组织收缩性测绘的扩张型心肌病患者衍生的三维心脏芯片模型

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 Epub Date: 2026-07-25 DOI: 10.1002/adhm.71464

Ali Mousavi, Ludovic Mouttet, Shihao Cui, Yasaman Hekmatnia, Mehran Mottahedi, Ida Derish, Naimeh Rafatian, Mark Aurousseau, Gregor Andelfinger, Renzo Cecere, Houman Savoji

{"title":"Patient-Derived 3D Heart-On-a-Chip Model of Dilated Cardiomyopathy With Embedded Bead-Based Mapping of Tissue Contractility","authors":"Ali Mousavi, Ludovic Mouttet, Shihao Cui, Yasaman Hekmatnia, Mehran Mottahedi, Ida Derish, Naimeh Rafatian, Mark Aurousseau, Gregor Andelfinger, Renzo Cecere, Houman Savoji","doi":"10.1002/adhm.71464","DOIUrl":"10.1002/adhm.71464","url":null,"abstract":"<p>Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation, with a 50% risk of progression to heart failure within 5 years. Conventional disease modeling approaches fail to recapitulate the sophisticated function of the human heart. Alternatively, heart-on-a-chip (HOC) platforms enable real-time monitoring of disease progression and drug responses using miniaturized engineered heart tissues. Here, we developed a functional HOC model using patient-specific human induced pluripotent stem cells (hiPSCs), reprogrammed from the patients’ blood samples. The chip contains two cell-seeding chambers with flexible silicone pillars to support tissue formation. Healthy and DCM hiPSCs were differentiated into cardiomyocytes, combined with an optimized ratio of human cardiac fibroblasts, encapsulated in a fibrin/Geltrex hydrogel (containing fluorescent beads), and seeded in the device chambers. The tissue gradually compacted and started beating spontaneously. Immunofluorescence assay revealed structural abnormalities in DCM tissues, including reduced cell alignment and elongation. The tissue functional responses (e.g., calcium transients and beating) were investigated after 2 weeks of culture, revealing arrhythmia-like behavior in DCM tissue and highlighting functional hallmarks of the disease. Finally, the platform was validated using norepinephrine to assess the functional responsiveness of the tissues. These results demonstrate the potential of this system for disease modeling and future patient-specific investigations.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.71464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Skin-Inspired Ti3C2Tx MXene-AgNWs/Silk Fibroin Composite Film for Skin Bioelectronics and Wound Management 皮肤启发Ti3C2Tx MXene-AgNWs/丝素复合膜用于皮肤生物电子学和伤口管理。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 Epub Date: 2026-08-28 DOI: 10.1002/adhm.71658

Shuyu Wang, Zhe Fu, Jingwen Zhang, Yutong Wu, Jingyu Jiang, Rui Liu, Wen Guo, Bingjie Mai, Xinwang Yang, Ziwei Deng

{"title":"Skin-Inspired Ti3C2Tx MXene-AgNWs/Silk Fibroin Composite Film for Skin Bioelectronics and Wound Management","authors":"Shuyu Wang, Zhe Fu, Jingwen Zhang, Yutong Wu, Jingyu Jiang, Rui Liu, Wen Guo, Bingjie Mai, Xinwang Yang, Ziwei Deng","doi":"10.1002/adhm.71658","DOIUrl":"10.1002/adhm.71658","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin bioelectronics have demonstrated significant potential in healthcare monitoring and wound management. Nevertheless, developing an innovative bioelectronics-integrated wound dressing still poses a significant clinical challenge in wound management. Herein, we present a smart and flexible bioelectronics-integrated wound dressing, constructed from a skin-inspired Ti<sub>3</sub>C<sub>2</sub>T<sub>x</sub> MXene-AgNWs/silk fibroin (MX-Ag/SF) composite film. The MX-Ag/SF composite film exhibits high breathability, conductivity, flexibility and stretchability, biocompatibility, and photothermal antibacterial properties. This makes it suitable for assembly into a versatile epidermal sensor for real-time monitoring of various human physiological signals. Furthermore, both in vitro and in vivo studies demonstrate that the MX-Ag/SF composite film significantly enhances its therapeutic efficacy in treating diabetic wounds, which is accomplished by suppressing inflammatory cell infiltration, promoting angiogenesis, enhancing re-epithelialization, stimulating collagen deposition, inhibiting bacterial growth, and effectively controlling wound infection. In addition, the MX-Ag/SF composite film functions as a novel flexible bioelectronic device for wound movement tracking or wound monitoring during wound healing process. This capability renders it highly promising for applications in skin bioelectronics for intelligent post-wound monitoring and rehabilitation motion management. This study introduces a promising approach to developing an innovative bioelectronics-integrated wound dressing, which can be applicable in skin bioelectronics for health monitoring and chronic wound management.</p>\u0000 </div>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849448","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}

引用次数: 0

Tailoring Metal Coordination in MOF-Based Triple-Layered Sealants for Gastric Hemostasis 基于mof的三层胃止血胶的金属配位调整。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 Epub Date: 2026-08-27 DOI: 10.1002/adhm.71653

Ruoyun Zhang, Xinyi Mao, Meiqi Wang, Luyao Zhang, Wenge Chen, Deyi Zhang, Zhangjie Pu, Guoqiang Li, Zhenzhen Zhu, Binglin Bie, Zhaowei Zhang

{"title":"Tailoring Metal Coordination in MOF-Based Triple-Layered Sealants for Gastric Hemostasis","authors":"Ruoyun Zhang, Xinyi Mao, Meiqi Wang, Luyao Zhang, Wenge Chen, Deyi Zhang, Zhangjie Pu, Guoqiang Li, Zhenzhen Zhu, Binglin Bie, Zhaowei Zhang","doi":"10.1002/adhm.71653","DOIUrl":"10.1002/adhm.71653","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastric perforation is one of the most difficult hemostatic scenes due to the extreme acidic environment, fragile tissue structure, and high risk of perforation leakage. A new series of sealants named M-MOF-74@Gel (M = Mg, Co, Ni, Cu, Zn) is invented for gastric perforation using a triple-layered design including the exterior antibacterial layer, the middle layer of soft scaffold, and the interior thrombin-like layer. Among these sealants, Zn-MOF-74@Gel sealant exhibits excellent biocompatibility near 95%, high efficiency of bacterial clearance (83.9% for <i>Escherichia coli</i>, 83.7% for <i>Staphylococcus aureus</i>), strong adhesion (94 kPa), and fast hemostasis for liver and gastric perforation (60 s for liver, 100 s for gastric perforation). In addition, MOF-74@Gel sealant can avoid the residue of MOF powder in trauma, adjust to the tissue shape, and inhibit the penetration of exterior aqueous solution. And the in vivo experiments further demonstrate the long-standing flexibility in gastric perforation with adhesive block, resulting in no obvious leakage in the perforation channel. These enable the rats to successfully survive after surgery without dependence on antibiotics, indicating great potential for MOF-74@Gel sealant in gastric perforation hemostasis.</p>\u0000 </div>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823832","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}

引用次数: 0

Rational Control of Antibody Orientation for Enhancing Sensitivity and Specificity in Lateral Flow Immunoassays With Clinical Validation. 合理控制抗体取向以提高侧流免疫测定的敏感性和特异性及临床验证。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 DOI: 10.1002/adhm.71815

Pin-Hao Wang, Shunmuga Nathan Shunmuga Nainar, Bing-Han Zhuang, Shun-Mao Yang, Hong-Cheu Lin, Yang-Hsiang Chan

{"title":"Rational Control of Antibody Orientation for Enhancing Sensitivity and Specificity in Lateral Flow Immunoassays With Clinical Validation.","authors":"Pin-Hao Wang, Shunmuga Nathan Shunmuga Nainar, Bing-Han Zhuang, Shun-Mao Yang, Hong-Cheu Lin, Yang-Hsiang Chan","doi":"10.1002/adhm.71815","DOIUrl":"https://doi.org/10.1002/adhm.71815","url":null,"abstract":"<p><p>Lateral flow assays (LFAs) are widely used for point-of-care diagnostics, but their sensitivity is often limited by inefficient antibody orientation and poor signal transduction. Herein, we report a universal strategy integrating orientation-controlled antibody conjugation at the immunoprobe with a biotin-streptavidin-modified test line to enhance LFA sensitivity, specificity, and analytical reliability. Using an orientation-controlled conjugation approach (P-6, Scheme 1), antigen accessibility was maximized while nonspecific adsorption and false-positive signals were suppressed. Compared with conventional randomly conjugated probes (P-3, Scheme 1) on unmodified test lines, the combined P-6/biotin-streptavidin configuration achieved limits of detection of 0.0352 ng/mL for cytokeratin 19 fragment (CYFRA21-1) and 0.0808 ng/mL for carcinoembryonic antigen (CEA), corresponding to sensitivity enhancements of approximately 14-19 fold. However, probe rankings get inverted across capture chemistries, indicating the importance of dual-site orientation. The universality of this strategy was further validated using alpha-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), and prostate-specific antigen (PSA). Furthermore, multiplexed LFAs using fluorescent polymer dots enabled simultaneous detection of CYFRA21-1 and CEA with minimal cross-reactivity and were validated in 28 clinical serum samples against the hospital reference method.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e71815"},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134280","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}

引用次数: 0

Multifunctional pH-Responsive Gelatin/Agarose Hydrogels Incorporating Gum Arabic for Wound Repair 含有阿拉伯胶的多功能ph响应明胶/琼脂糖水凝胶用于伤口修复。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 Epub Date: 2026-09-01 DOI: 10.1002/adhm.71654

Z. Ghasemi, K. Mohagheghiyan, M. Kharaziha, M. Shokri, S. M. Ahmadi Tafti

{"title":"Multifunctional pH-Responsive Gelatin/Agarose Hydrogels Incorporating Gum Arabic for Wound Repair","authors":"Z. Ghasemi, K. Mohagheghiyan, M. Kharaziha, M. Shokri, S. M. Ahmadi Tafti","doi":"10.1002/adhm.71654","DOIUrl":"10.1002/adhm.71654","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to develop pH-sensitive GelAgar-GA hydrogels composed of Gum Arabic (GA)-incorporated gelatin and agarose for wound healing applications. Our results reveal that the agarose content modulates the structural, chemical, physical, and biological properties of hydrogels. Noticeably, the hydrogel containing 3 wt% agarose (GelAgar-GA-3) shows optimized characteristics, including superior elastic modulus (186 ± 12 kPa) and tensile strength (173 ± 12 kPa), mimicking the mechanical properties of native skin. The swelling ability of this hydrogel is modulated via pH changes. Noticeably, the water absorption capacity of GelAgar-GA-3 at pH = 5 is 247 ± 47%, which increases to 327±45% at pH = 9. GelAgar-GA hydrogels also indicate significant coagulation ability, low hemolysis (<5%), and decreased bleeding compared to the control. In vitro studies reveal that GelAgar-GA hydrogel could accelerate the proliferation and migration of fibroblasts and shows significant antibacterial activity, following doxycycline encapsulation (GelAgar-GA-3(Dox)). In vivo studies on a rat model also show 99% wound closure in full-thickness wounds treated with GelAgar-GA-3(Dox), attributed to the reduced inflammatory response and promoted vascular remodeling, maturation, and collagen deposition, thereby resulting in accelerated wound repair. In summary, these results demonstrate that the GelAgar-GA-3(Dox) is a favorable system for wound healing applications.</p>\u0000 </div>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872247","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}

引用次数: 0

Targeted Lactic Acid Regulation via Engineered Exosomes for Synergistic Metabolic and Photodynamic Tumor Therapy 通过工程外泌体靶向乳酸调控用于协同代谢和光动力肿瘤治疗。

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 Epub Date: 2026-08-28 DOI: 10.1002/adhm.71659

Sisi Zhou, Yu Cao, Xianbiao Wang, Songqin Liu

{"title":"Targeted Lactic Acid Regulation via Engineered Exosomes for Synergistic Metabolic and Photodynamic Tumor Therapy","authors":"Sisi Zhou, Yu Cao, Xianbiao Wang, Songqin Liu","doi":"10.1002/adhm.71659","DOIUrl":"10.1002/adhm.71659","url":null,"abstract":"<div>\u0000 \u0000 <p>Tumor cells exhibit a hyper-glycolytic phenotype, resulting in massive lactic acid (LA) production that acidifies the tumor microenvironment (TME) and fosters immunosuppression. Current lactate-targeted therapies often lack synergistic dual-directional regulation. Herein, we engineer an exosomal nanoplatform, PpIX/siRNA@EXO-LOD, to simultaneously disrupt intra- and extracellular LA homeostasis, thereby enabling synergistic metabolic and photodynamic therapy (PDT). The system integrates three key components: protoporphyrin IX (PpIX) for PDT, siRNA targeting monocarboxylate transporter 4 (MCT4) for intracellular metabolic interference, and surface-displayed lactate oxidase (LOD) for extracellular catalytic starvation. Upon epithelial cell adhesion molecule (EpCAM)-mediated targeting, the nanovesicle triggers a cascade of synergistic effects. Crucially, siRNA-mediated silencing of MCT4 induces lethal intracellular acidosis, leading to significant intracellular H<sub>2</sub>O<sub>2</sub> accumulation. This elevated H<sub>2</sub>O<sub>2</sub> level acts as a booster for PpIX-generated reactive oxygen species (ROS) upon laser irradiation, creating an amplified oxidative stress burst that overwhelms tumor cell defenses. Concurrently, surface-anchored LOD consumes extracellular LA, alleviates lactate-induced immunosuppression. In vivo studies demonstrate that this dual-regulation strategy effectively inhibits tumor growth, downregulates metastasis-related factors (amphiregulin (AREG), ATP-binding cassette sub-family B member 1 (ABCB1)), and reprograms the TME from an immunosuppressive state to an immunologically active state. This work presents a precision nanomedicine strategy that leverages the interplay between metabolic modulation and photodynamic amplification for enhanced cancer treatment.</p>\u0000 </div>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849465","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}

引用次数: 0

Lipopolymer Nanoparticle-Mediated In Vivo CRISPR-Cas9 Editing of Mrg15 Restores Mitochondrial Mitophagy to Alleviate Metabolic-Associated Steatohepatitis 脂聚合物纳米颗粒介导的体内CRISPR-Cas9编辑Mrg15恢复线粒体自噬以减轻代谢相关脂肪性肝炎

IF 11 2区医学

Advanced Healthcare Materials Pub Date : 2026-10-09 Epub Date: 2026-08-31 DOI: 10.1002/adhm.71652

Zixi Zhang, Jing Liao, Tingfeng Yu, Sijie Chen, Ling Zeng, Guanzi Chen, Qian Shen, Yingsen Tang, Meng Jiang, Jinjin Chen, Lingyun Wang

{"title":"Lipopolymer Nanoparticle-Mediated In Vivo CRISPR-Cas9 Editing of Mrg15 Restores Mitochondrial Mitophagy to Alleviate Metabolic-Associated Steatohepatitis","authors":"Zixi Zhang, Jing Liao, Tingfeng Yu, Sijie Chen, Ling Zeng, Guanzi Chen, Qian Shen, Yingsen Tang, Meng Jiang, Jinjin Chen, Lingyun Wang","doi":"10.1002/adhm.71652","DOIUrl":"10.1002/adhm.71652","url":null,"abstract":"<div>\u0000 \u0000 <p>Metabolic-associated steatohepatitis (MASH) remains difficult to treat due to the lack of interventions capable of targeting upstream disease drivers and achieving durable disease modification. The epigenetic regulator Mrg15 has been implicated in mitochondrial dysfunction and metabolic stress in the liver, suggesting its potential relevance to MASH pathogenesis. Here, we develop a liver-targeted lipopolymer nanoparticle (LPNP)-mediated gene editing platform to enable in vivo disruption of Mrg15 by co-delivery of Cas9 mRNA and Mrg15 sgRNA. The screened P64H/Mrg15 system achieved efficient hepatic delivery and genome editing, resulting in reduced Mrg15 expression in hepatocytes. In the MASH mouse model, P64H/Mrg15 treatment was associated with decreased hepatic lipid accumulation, improved liver injury markers, and attenuation of inflammation and fibrosis. Sequence-level analyses confirmed on-target editing in liver tissue, and systemic histopathological evaluation revealed no overt toxicity in major organs under the tested dosing regimen. Transcriptomic profiling revealed coordinated pathway-level associations involving metabolic, inflammatory, and autophagy-related regulation, while protein-level analyses demonstrated alterations in selected autophagy- and mitophagy-related regulators, including TUFM and LC3B-II. Together, these findings identify Mrg15 as a disease-relevant epigenetic regulator in MASH and highlight liver-directed P64H LPNP/CRISPR delivery as a promising non-viral strategy for modulating upstream regulatory pathways in metabolic liver disease.</p>\u0000 </div>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"15 37","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862681","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}

引用次数: 0