Advanced Healthcare Materials最新文献_第10页

Tumor Microenvironment-Responsive Hydrogen-Generating Zn-Doped ReZIF-8 Nanoplatform for Enhanced Tumor Suppression. 肿瘤微环境响应产氢锌掺杂ReZIF-8纳米平台增强肿瘤抑制。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-13 DOI: 10.1002/adhm.202502489

Kexin Qin, Zitong Zheng, Yuemin Zhou, Xingcan Shen, Ruikang Tang, Xiaoyu Wang

{"title":"Tumor Microenvironment-Responsive Hydrogen-Generating Zn-Doped ReZIF-8 Nanoplatform for Enhanced Tumor Suppression.","authors":"Kexin Qin, Zitong Zheng, Yuemin Zhou, Xingcan Shen, Ruikang Tang, Xiaoyu Wang","doi":"10.1002/adhm.202502489","DOIUrl":"https://doi.org/10.1002/adhm.202502489","url":null,"abstract":"Hydrogen-based tumor therapy demonstrates therapeutic potential, while the efficacy remains limited by insufficient intracellular hydrogen generation, poorly controlled release kinetics, and inadequate immune response potentiation. To address these limitations, a partially reduced zinc-doped zeolitic imidazolate framework-8 (ReZIF-8) is developed, functioning as a dual-functional nanoplatform for both intracellular hydrogen generation and controlled Zn(II) ions (Zn2+) overload. The cationic surface charge of ReZIF-8 enhances cellular internalization, while its pH-responsive properties facilitate controlled intracellular hydrogen gas (H2) release. The accumulated H2 and Zn2+ overload act synergistically to disrupt redox homeostasis in tumor cells, inducing reactive oxygen species (ROS)-dependent immunogenic cell death (ICD). This ICD activation robustly stimulates innate immune responses and enhances antigen cross-presentation. Intratumoral administration of ReZIF-8 in a B16F10 melanoma mouse model elicits potent antitumor efficacy via intracellular H2-triggered terminal differentiation and cell cycle arrest. The therapeutic effect is further enhanced in combination with αPD-1 immune checkpoint blockade, resulting in extended survival and significant suppression of metastatic progression, highlighting its translational potential. The ReZIF-8-mediated H2-generating nanoplatform reprograms intratumoral redox balance to simultaneously induce ICD, amplify antitumor immunity, and drive terminal differentiation. This triple-pronged mechanism leverages synergistic modulation to achieve comprehensive tumor control.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02489"},"PeriodicalIF":9.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051480","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

Injectable ROS-Scavenging Trimetallic Nanocomposite Hydrogel Modulates Oxidative Microenvironment for Treatment of Intervertebral Disc Degeneration. 可注射清除ros的三金属纳米复合水凝胶调节氧化微环境治疗椎间盘退变。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-12 DOI: 10.1002/adhm.202501662

Linjun Yang, Zhanqiu Dai, Xuhui Fan, Yao Jin, Jianle Wang, Congcong Yu, Han Wang, Zhijun Hu

{"title":"Injectable ROS-Scavenging Trimetallic Nanocomposite Hydrogel Modulates Oxidative Microenvironment for Treatment of Intervertebral Disc Degeneration.","authors":"Linjun Yang, Zhanqiu Dai, Xuhui Fan, Yao Jin, Jianle Wang, Congcong Yu, Han Wang, Zhijun Hu","doi":"10.1002/adhm.202501662","DOIUrl":"https://doi.org/10.1002/adhm.202501662","url":null,"abstract":"As a central driver of intervertebral disc degeneration (IVDD), oxidative stress mediates pathological changes by promoting extracellular matrix (ECM) breakdown, thereby accelerating the degenerative process. To target this pathological cascade, trimetallic nanoparticles (TriNPs) are designed and developed to modulate the oxidative microenvironment of intervertebral discs and restore ECM homeostasis through reactive oxygen species (ROS) scavenging. In vitro studies demonstrate that TriNPs provide significant cytoprotection against H2O2-induced oxidative damage in nucleus pulposus (NP) cells through efficient ROS elimination. For translational applications, TriNPs are encapsulated within an injectable hydrogel (termed TOH) to evaluate their therapeutic potential in a rat IVDD model. In vivo studies encompassing both radiographic and histomorphometric analyses reveal that TOH administration significantly improves the Disc Height Index (DHI) and T2-weighted Magnetic Resonance Imaging (MRI) grading, while also reducing histological scores. Collectively, these results indicate that TOH may serve as an innovative therapeutic approach to modulate disc microenvironment and attenuate IVDD progression.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01662"},"PeriodicalIF":9.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038675","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

Customized Design and Preparation of Bionic Drug Delivery System Leveraging Single-Cell RNA Sequencing for Precisely Targeted Therapy. 利用单细胞RNA测序进行精确靶向治疗的仿生给药系统的定制设计和制备。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-12 DOI: 10.1002/adhm.202501497

Tong Yu, Yeqing Wang, Yi Kong, Jianwei Wang, Hong Yun, Yunchao Wang, Fuqiang Hu, Zhongxin Zhu, Hong Yuan

{"title":"Customized Design and Preparation of Bionic Drug Delivery System Leveraging Single-Cell RNA Sequencing for Precisely Targeted Therapy.","authors":"Tong Yu, Yeqing Wang, Yi Kong, Jianwei Wang, Hong Yun, Yunchao Wang, Fuqiang Hu, Zhongxin Zhu, Hong Yuan","doi":"10.1002/adhm.202501497","DOIUrl":"https://doi.org/10.1002/adhm.202501497","url":null,"abstract":"Drug delivery system (DDS) is an important branch of pharmaceutics. Rational modification of the physicochemical properties of DDSs can further improve their targeting efficiency. Herein, a bionic DDS is reported for AKI that is scRNA-seq-guided, custom-designed, and prepared, targeting the Key Cell Subtype for Pathological Progression (KCS-PP) of acute kidney injury (AKI). Specifically, scRNA-seq is utilized to identify a specific renal tubular epithelial cell subtype (PTIs) as the KCS-PP for AKI from numerous cellular subtypes. Additionally, specific cell adhesion molecules (VCAM1 and ICAM1) are identified as the Targeting Drug Delivery Mediators (TDDMs) for PTIs from a list of 1000 marker genes of PTIs. Based on this progress, PTI-targeting bionic DDS, named BRNCs@AMMOs is custom-designed and prepared, and used them for AKI treatment in vitro and in vivo. In vitro, BRNCs@AMMOs shows that its adhesion ability in PTI model cells is 3.2 times that in normal cells. In vivo, 6 h after renal pelvis injection, the MFI of BRNCs@AMMOs-DiI in AKI kidneys is 3.7 times that of sham kidneys. The findings demonstrate that BRNCs@AMMOs exhibits prolonged retention in PTI model cells and AKI kidneys. Overall, the custom-designed and prepared PTI-targeting bionic DDS, may promote the customized design and preparation of DDSs for different diseases and targets, is reported.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01497"},"PeriodicalIF":9.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038671","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

Programmable Compliance in Small-Diameter Vascular Grafts by Design of Melt-Electrowritten Scaffold Architectures for In Situ Tissue Engineering. 基于原位组织工程的熔融电写支架结构设计在小直径血管移植物中的可编程顺应性。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-12 DOI: 10.1002/adhm.202502038

Kilian Maria Arthur Mueller, Christina Ahrens, Linda Grefen, Salma Mansi, Dario Arcuti, Elena De-Juan-Pardo, Felix Kur, Christian Hagl, Petra Mela

{"title":"Programmable Compliance in Small-Diameter Vascular Grafts by Design of Melt-Electrowritten Scaffold Architectures for In Situ Tissue Engineering.","authors":"Kilian Maria Arthur Mueller, Christina Ahrens, Linda Grefen, Salma Mansi, Dario Arcuti, Elena De-Juan-Pardo, Felix Kur, Christian Hagl, Petra Mela","doi":"10.1002/adhm.202502038","DOIUrl":"https://doi.org/10.1002/adhm.202502038","url":null,"abstract":"In clinical practice, synthetic vascular grafts are advantageous due to their immediate availability but are burdened by high failure rates in small-diameter settings because of thrombogenicity, infections, and intimal hyperplasia (IH). A mismatch in compliance between graft and host vessel has been identified as a major contributor to the development of IH. Here, we propose a design strategy to fabricate polymeric small-diameter vascular graft scaffolds with programmable compliance based on a helical microfiber architecture via melt electrowriting (MEW). By controlling the fiber winding angle, this design strategy exploits, for the first time, the mechanical structure-function relationship of MEW scaffolds to enable tailored compliance covering the physiological range of arteries and veins. This concept is complemented by an integrated microporous MEW graft wall, potentially enabling in situ tissue engineering to combine the advantages of synthetic (off-the-shelf) and autologous (living) grafts. Leveraging this, a gradient is introduced in the fiber architecture to achieve arteriovenous grafts matching the compliance of the target vessels at their ends (arterial vs. venous compliance) with a continuous smooth transitional region in between. The potential for clinical translation is demonstrated in vitro by assessing suture-retention strength, anti-kinking properties, burst pressure, and cannulation behavior.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02038"},"PeriodicalIF":9.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038643","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

Thiolated Hyaluronic Acid: A Gateway for Targeted Killing of Staphylococcus aureus on the Race for Surface Colonization. 硫代透明质酸：一种靶向杀死金黄色葡萄球菌表面定植的途径。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-12 DOI: 10.1002/adhm.202502890

Mariana Blanco Massani, Susanne Meile, Annabelle Knoll, David Gintsburg, Ilaria Polidori, Anna Seybold, Débora C Coraça-Huber, Martin J Loessner, Gergely Kali, Mathias Schmelcher, Szczepan Zapotoczny, Andreas Bernkop-Schnürch

{"title":"Thiolated Hyaluronic Acid: A Gateway for Targeted Killing of Staphylococcus aureus on the Race for Surface Colonization.","authors":"Mariana Blanco Massani, Susanne Meile, Annabelle Knoll, David Gintsburg, Ilaria Polidori, Anna Seybold, Débora C Coraça-Huber, Martin J Loessner, Gergely Kali, Mathias Schmelcher, Szczepan Zapotoczny, Andreas Bernkop-Schnürch","doi":"10.1002/adhm.202502890","DOIUrl":"https://doi.org/10.1002/adhm.202502890","url":null,"abstract":"Hyaluronic acid (HA) is degraded by Staphylococcal hyaluronate lyase (Hysa) and mammalian hyaluronidase (Hyal). Thiolated HA (HAMS) is used as a targeted gateway for Staphylococcus aureus killing while enhancing the previous M23 endolysin-polyphosphate (M23-PP NPs) enzyme-responsive nanoparticle formulation. Synthesis of HAMS and characterization for nuclear magnetic resonance, solubility, thiol content, pKa, and degradation by Hysa and Hyal are presented. Nanoparticles prepared via ionotropic gelation between M23-PP NPs and either HAMS or HA yield M23-PP/HAMS or M23-PP/HA NPs, respectively. Their characterization includes size, zeta potential, morphology, release profiles, safety, targeted release, and efficacy. HAMS with a thiol content of 250.18 ± 90.32 µmol g-1, solubility of 50.99 ± 0.02 mg mL-1, exhibits pKa values of 3.2, 4.2, and 8.8. This thiolated polymer irreversibly inhibits Hyal activity, without affecting Hysa. M23-PP/HAMS NPs (265 ± 47 nm, -25 mV) maintain their integrity for seven days at 37 °C, and HAMS coating prevents nonspecific degradation by Hyal, as confirmed by release studies. In a co-culture 'race for the surface' experiment with MC3T3 osteoblasts and S. aureus ATCC 25923, M23-PP/HAMS NPs produce 8-log bacterial killing while promoting in vitro wound healing. These findings are pivotal to the development of new enzyme-responsive excipients switchable by S. aureus.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02890"},"PeriodicalIF":9.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038694","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

Stretchable Multilevel Mesh Brain Electrodes for Neuroplasticity in Glioma Patients Undergoing Surgery. 可拉伸多层网状脑电极用于神经胶质瘤手术患者的神经可塑性。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-12 DOI: 10.1002/adhm.202503358

Yafeng Liu, Guangyuan Xu, Chunzhao Li, Yinji Ma, Nan Ji, Xue Feng

{"title":"Stretchable Multilevel Mesh Brain Electrodes for Neuroplasticity in Glioma Patients Undergoing Surgery.","authors":"Yafeng Liu, Guangyuan Xu, Chunzhao Li, Yinji Ma, Nan Ji, Xue Feng","doi":"10.1002/adhm.202503358","DOIUrl":"https://doi.org/10.1002/adhm.202503358","url":null,"abstract":"Brain disease surgical treatment usually leads to neurological dysfunction. Electroencephalogram (EEG)-based neuroplasticity study may facilitate patient nerve function recovery from injury, allowing a return to normal activities. Due to the limitations of wound infections and hair barrier effects, a traditional brain-computer interface system is not applicable to patients after tumor resection. Here, stretchable multilevel mesh brain electrodes with reconfigurable interfaces are developed. The electrode has a multilevel mesh and malleable structure to avoid hair blockage between the electrode and scalp, realizing the conformal attachment of the stretchable multilevel mesh brain electrodes to a nondevelopable curved brain surface. Moreover, the thermally reversible hydrogel forms a good reconfigurable interface contact between the electrode and scalp, reducing postoperative infection and secondary injury risks to ensure the high-quality acquisition EEGs. In this study, a newly invented stretchable multilevel mesh brain electrodes is applied to test the preoperative and postoperative EEGs of recurrent glioblastoma patients for the first time. The obvious inhibitory effects of tumors on brain activity (a-wave signals) are discovered. More importantly, the EEG signals gradually enhance with postoperative recovery, which is mutually confirmed with the Karnofsky score results, showing the possibility of neural function remodeling neurological rehabilitation in adults.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03358"},"PeriodicalIF":9.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038649","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

Democratizing Organ-On-Chip Technologies With a Modular, Reusable, and Perfusion-Ready Microphysiological System. 民主化器官芯片技术与模块化，可重复使用，和灌注就绪微生理系统。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-10 DOI: 10.1002/adhm.202502202

Daniel J Minahan, Katherine M Nelson, Filipa Ribeiro, Bryan J Ferrick, Alexandra M Zurzolo, Kira Byers, Victoria Mckeown, Jason P Gleghorn

{"title":"Democratizing Organ-On-Chip Technologies With a Modular, Reusable, and Perfusion-Ready Microphysiological System.","authors":"Daniel J Minahan, Katherine M Nelson, Filipa Ribeiro, Bryan J Ferrick, Alexandra M Zurzolo, Kira Byers, Victoria Mckeown, Jason P Gleghorn","doi":"10.1002/adhm.202502202","DOIUrl":"10.1002/adhm.202502202","url":null,"abstract":"Organ-on-chip (OOC) technologies, also called microphysiological systems (MPS), offer dynamic microenvironments that improve upon static culture systems, yet widespread adoption has been hindered by fabrication complexity, reliance on polydimethylsiloxane (PDMS), and limited modularity. Here, a modular MPS platform is presented, designed for ease of use, reproducibility, and broad applicability. The system comprises layered elastomeric inserts for dual monolayer cell culture, which is clamped within a reusable acrylic cassette for perfusion studies. This enables researchers to decouple model establishment from flow experiments and streamline their workflows. The system is validated using dual epithelial and endothelial cell co-culture under static and perfused conditions, including shear-induced alignment of HUVECs. Material testing confirmed biocompatibility, while vinyl cutting reproducibility demonstrated high manufacturing fidelity. The platform reliably supported long-term culture (up to 14 days), and the open insert format facilitated uniform seeding and imaging access. This approach enables parallelized experimentation, minimizes pump usage, and is well-suited for labs without microfabrication infrastructure. By combining fabrication flexibility with biological robustness, this work establishes a generalizable platform for modular tissue-chip development adapted to diverse organ systems and serves as a foundational framework for democratizing advanced in vitro model systems.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02202"},"PeriodicalIF":9.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032602","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

A Novel Nanozyme-based Coordination Compound for Synergistic Periprosthetic Joint Infection Treatment and Bone Repair. 一种新型纳米酶配合物用于假体周围关节感染的协同治疗和骨修复。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-10 DOI: 10.1002/adhm.202502379

Siyu Yang, Siyu Li, Long Zhang, Mingqi Zhao, Tingbin Zhang, Xin Liu, Bo Liu, Hongze Zhang, Yiqian Gong, Huan Zhou, Huipeng Li, Lei Yang

{"title":"A Novel Nanozyme-based Coordination Compound for Synergistic Periprosthetic Joint Infection Treatment and Bone Repair.","authors":"Siyu Yang, Siyu Li, Long Zhang, Mingqi Zhao, Tingbin Zhang, Xin Liu, Bo Liu, Hongze Zhang, Yiqian Gong, Huan Zhou, Huipeng Li, Lei Yang","doi":"10.1002/adhm.202502379","DOIUrl":"https://doi.org/10.1002/adhm.202502379","url":null,"abstract":"Periprosthetic joint infection (PJI) represents a serious complication following joint arthroplasty, and it often results in implant failure, prolonged morbidity, and additional healthcare burdens. Current clinical strategies for PJI treatment face obstacles, including antibiotic resistance, high recurrence rate, and compromised bone repair. To address these challenges, a novel nanozyme-based coordination compound designated as W-GA-Van@Zn is developed. Gallic acid decorated tungsten nanozyme (W-GA) with dual photothermal and reactive oxygen species (ROS) scavenging ability is chosen as the core of W-GA-Van@Zn, and vancomycin as a bacterial targeting agent is decorated on W-GA surface using amide reaction. After that, zinc ions are introduced and formed a metal-phenolic coordination compound across by the polyphenolic groups on the nanozyme surface. W-GA-Van@Zn could achieve bacterial targeting ability through specific binding to D-Ala-D-Ala moieties on the bacterial surface, and realize synergistic PJI treatment combining mild photothermal therapy (PTT) and antibiotic therapy. Meanwhile, the nanozyme could simultaneously scavenge PTT-generated ROS, overcoming the side effect during PTT treatment. Besides, PTT-antibiotic combination therapy reduced antibiotic dosage and provided excellent bactericidal efficacy at low antibiotic concentrations. During the bone repair stage post-PJI treatment, the nanozyme sustained ROS scavenging to reduce inflammatory microenvironment, together with zinc ions for synergistic bone repairment.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02379"},"PeriodicalIF":9.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032615","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

A Transformable Nanoplatform Precisely Positions Fibroblast-Like Synoviocytes via FAP-α for Improved Rheumatoid Arthritis Therapy. 可转化纳米平台通过FAP-α精确定位成纤维细胞样滑膜细胞，改善类风湿关节炎治疗。

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-10 DOI: 10.1002/adhm.202503277

Chenglong Li, Shuhao Xu, Xin Li, Huaiyu Su, Can Qian, Yingying Hou, Sanjun Shi

{"title":"A Transformable Nanoplatform Precisely Positions Fibroblast-Like Synoviocytes via FAP-α for Improved Rheumatoid Arthritis Therapy.","authors":"Chenglong Li, Shuhao Xu, Xin Li, Huaiyu Su, Can Qian, Yingying Hou, Sanjun Shi","doi":"10.1002/adhm.202503277","DOIUrl":"https://doi.org/10.1002/adhm.202503277","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, damage, and disability. Activated fibroblast-like synoviocytes (FLSs), abundant in RA synovium, crucially facilitate disease progression. These activated FLSs drive RA pathogenesis by upregulating adhesion molecules, proinflammatory cytokines, chemokines, and major histocompatibility complex class II (MHC-II). This upregulation facilitates their interaction with CD4+ T cells, triggering an inflammatory cascade that exacerbates synovial inflammation. To address this, a DSPE-mPEG2000-GPA-KLVFF-decorated liposome loaded with dexamethasone (DPGK@Lipo-Dex) is developed to precisely target FLSs in arthritic joints. DPGK@Lipo-Dex achieves efficient binding to FLSs through a specific enzymatic interaction between fibroblast activation protein-α (FAP-α) and GPA, along with prolonged retention in the joints due to the fibrillar transformation of KLVFF. In vitro studies demonstrate that DPGK@Lipo-Dex enhances cellular uptake and reduces MHC-II expression on aggressive FLSs. In adjuvant-induced arthritis (AIA) rats, DPGK@Lipo shows specific distribution patterns that target both inflamed joints and FLSs. Treatment with DPGK@Lipo-Dex leads to a downregulation of MHC-II expression, a decrease in the number of activated T cells within the synovium, and a reduction in levels of proinflammatory mediators. Overall, DPGK@Lipo-Dex effectively suppresses FLSs-related responses and ultimately results in inflammatory remission. This makes DPGK@Lipo-Dex a promising candidate for nano-therapeutic treatment in rheumatoid arthritis.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03277"},"PeriodicalIF":9.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032604","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

CD123 Targeted Epigenetic Nanotherapy for Fusion Oncoprotein MLL-AF9 Rearranged Acute Myeloid Leukemia in Preclinical and Patient Derived Xenograft Models. CD123靶向表观遗传纳米治疗融合癌蛋白MLL-AF9重排急性髓系白血病临床前和患者来源的异种移植模型

IF 9.6 2区医学

Advanced Healthcare Materials Pub Date : 2025-09-10 DOI: 10.1002/adhm.202503118

Avinash Chandra Kushwaha, Pankaj Malhotra, Surajit Karmakar, Subhasree Roy Choudhury

{"title":"CD123 Targeted Epigenetic Nanotherapy for Fusion Oncoprotein MLL-AF9 Rearranged Acute Myeloid Leukemia in Preclinical and Patient Derived Xenograft Models.","authors":"Avinash Chandra Kushwaha, Pankaj Malhotra, Surajit Karmakar, Subhasree Roy Choudhury","doi":"10.1002/adhm.202503118","DOIUrl":"https://doi.org/10.1002/adhm.202503118","url":null,"abstract":"Acute Myeloid Leukemia (AML) is a heterogeneous hematological malignancy with an altered bone marrow microenvironment sheltering leukemic stem cells (LSCs). LSCs are characterized as self-renewing and highly proliferative cancer stem cells and accumulate abnormal genetic and epigenetic factors contributing to their uncontrolled proliferation. Chromosomal translocation t(9;11)(p22;q23) forms fusion oncoprotein, MLL-AF9, and regulates the transcription factor, C-Myb, which is highly expressed in AML. C-Myb regulates polycomb protein, EzH2, but this is still unexplored in MLL-AF9-induced AML, which highly expresses CD123. The active targeting with epigenetic regulation of EzH2 in MLL-AF9-rearranged AML can provide novel translational potential for anti-AML therapeutics. So, CD123-targeted delivery of EzH2 siRNA is hypothesized through ZW25 aptamer-functionalized human serum albumin nanoparticles (si-EzH2@HNPs@ZW25) for enhanced anti-AML therapeutics in MLL-AF9-induced in vitro and in vivo AML models. si-EzH2@HNPs@ZW25 exhibit superior therapeutic efficacy under MLL-AF9-induced athymic xenografts with enhanced suppression of c-Kit+ LSCs, and stimulation of myeloid-specific differentiation markers, CD11b and Gr-1. si-EzH2@HNPs@ZW25 increased the survival of CD34+CD38- AML patient-derived xenograft mice and augmented the suppression of c-Kit+ LSCs and stimulation of CD11b and Gr-1. In MLL-AF9 AML, C-Myb directly regulates EzH2 through promoter binding wherein si-EzH2@HNPs@ZW25 disrupt this functional crosstalk in AML revealingfuture translational potential of si-EzH2@HNPs@ZW25 as AML therapy.","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03118"},"PeriodicalIF":9.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032611","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