Biomaterials最新文献

{"title":"Transforming malignant tumors into vulnerable phenotypes via nanoscale coordination polymer mediated cell senescence and photodynamic therapy","authors":"Wenyao Zhen ,&nbsp;Xiaomin Jiang ,&nbsp;En Li ,&nbsp;Tomas Germanas ,&nbsp;Morten J. Lee ,&nbsp;Taokun Luo ,&nbsp;Xin Ma ,&nbsp;Chaoyu Wang ,&nbsp;Yimei Chen ,&nbsp;Ralph R. Weichselbaum ,&nbsp;Wenbin Lin","doi":"10.1016/j.biomaterials.2025.123355","DOIUrl":"10.1016/j.biomaterials.2025.123355","url":null,"abstract":"<div><div>Induction of senescence in cancer cells can thwart the proliferation of malignant tumors. Herein we report the design of AZT-P/pyro nanoscale coordination polymer particles consisting of 3-azido-2,3-dideoxythymidine monophosphate (AZT-P) in the core and photosensitizing pyro-lipid (pyro) in the shell for potent antitumor treatment. Gradual release of AZT-P in response to an acidic tumor microenvironment transforms cancer cells with unlimited proliferation capacity into senescent cells that are vulnerable to reactive oxygen species (ROS). Pyro selectively induces ROS generation and immunogenic cell death of cancer cells upon light irradiation. Co-delivery of AZT-P and pyro in a single particle prolongs their blood circulation times and enhances their accumulation in tumors. Additionally, the induction of senescence and ROS generation both contribute to the recruitment of immune cells to the tumors, resulting in an effective immune response to inhibit the growth of large subcutaneous tumors and metastatic spread of orthotopic tumors.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123355"},"PeriodicalIF":12.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-specific activated polymeric nanotuners disrupt positive feedback cycle of hypoxia and apoptosis evasion for potent cancer radiotherapy","authors":"Xiaoxue Hou ,&nbsp;Chun Wang ,&nbsp;Yu Zhao ,&nbsp;Qian Wang ,&nbsp;Dianyu Wang ,&nbsp;Jingyu Zhao ,&nbsp;Yang Liu ,&nbsp;Fan Huang ,&nbsp;Jianfeng Liu","doi":"10.1016/j.biomaterials.2025.123361","DOIUrl":"10.1016/j.biomaterials.2025.123361","url":null,"abstract":"<div><div>Effective cancer radiotherapy is usually hindered by the self-perpetuating feedback cycle between tumor hypoxia and apoptosis evasion. Herein, a tumor-specific activated polymeric nanotuner is developed to boost radiotherapy outcomes by disrupting this vicious cycle. The designed nanotuner is composed of a proapoptotic peptide-engineered catalase core and a pH-detachable polymer shell. They can maintain the core-shell structure to against immune clearance and enzymatic degradation under the “turn-off” state. When reaching the tumor site, the nanotuners hold acid-responsive “turn-on” property by dissociating the polymeric shell, facilitating the tumor accumulation and cellular internalization of the exposed functional core. Subsequently, the internalized core of polymeric nanotuners efficiently decomposes endogenous hydrogen peroxide (H₂O₂) into oxygen (O₂) for hypoxia alleviation, thus upregulating the expression of proapoptotic protein Smac. Furthermore, the apoptotic-inducing peptide modified on the core surface further boosts the Smac-induced apoptosis signal, intervening in tumor apoptosis evasion and ultimately realizing the efficient radiotherapeutic efficiency by blocking this vicious cycle. In vivo studies demonstrated that treatment with polymeric nanotuners remarkably enhances radiation-mediated tumor ablation without perceptible side effects. This study sheds light on the innovative attempt to specifically interfere with the feedback cycle in tumor radioresistance, pioneering the way for achieving safe and efficient cancer therapies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123361"},"PeriodicalIF":12.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuneable gelatin methacryloyl (GelMA) hydrogels for the directed specification of renal cell types for hiPSC-derived kidney organoid maturation","authors":"Shane Clerkin ,&nbsp;Krutika Singh ,&nbsp;Jessica L. Davis ,&nbsp;Niall J. Treacy ,&nbsp;Ivan Krupa ,&nbsp;Emmanuel G. Reynaud ,&nbsp;Robert M. Lees ,&nbsp;Sarah R. Needham ,&nbsp;Delphi MacWhite-Begg ,&nbsp;Jacek K. Wychowaniec ,&nbsp;Dermot F. Brougham ,&nbsp;John Crean","doi":"10.1016/j.biomaterials.2025.123349","DOIUrl":"10.1016/j.biomaterials.2025.123349","url":null,"abstract":"<div><div>Diabetic Kidney Disease (DKD) represents a significant global health burden and is recognised as the leading cause of end-stage renal disease. Kidney organoids derived from human induced Pluripotent Stem Cells (hiPSCs) have the potential to transform how we model renal disease and may provide personalised replacement tissues for patients with renal failure. However, kidney organoids remain poorly reproducible, and are structurally and functionally immature. Three-dimensional cultures that more appropriately mimic the complexity of the <em>in vivo</em> microenvironment are required to improve organoid maturation and structural authenticity. Here, we describe the application of semi-synthetic Gelatin Methacryloyl (GelMA) hydrogels as extracellular support matrices for the differentiation of hiPSC-derived kidney organoids. Hydrogels of defined mechanical strengths were generated by varying the concentration of GelMA solution in the presence of low concentration photo-initiator. After confirming a high level of mechanical stability of the hydrogels over extended culture periods, their effect on kidney organoid maturation was investigated. Organoids differentiated within GelMA hydrogels generated typical renal cell types including podocytes, tubular epithelia, renal interstitial cells, and some nascent vascularisation. Interestingly, kidney organoids derived within hydrogels that closely approximate the stiffness of the adult human kidney (∼5000–10,000 Pa) demonstrated improved podocyte maturation and were shown to upregulate renal vesicle-associated genes at an earlier stage following encapsulation when compared to organoids derived within softer hydrogels (∼400 Pa). A model of TGFβ-induced injury was also developed to investigate the influence of the mechanical environment in propagating early, fibrotic-like features of DKD within organoids. Growth within the softer matrix was shown to reduce pSMAD3 expression following TGFβ1 treatment, and accordingly ameliorate the expression of the myofibroblast marker α-Smooth Muscle Actin (α-SMA). This work demonstrates the suitability of GelMA hydrogels as mechanically-stable, highly-tuneable, batch-to-batch reproducible three-dimensional supports for hiPSC-derived kidney organoid growth and differentiation, and further substantiates the role of the biophysical environment in guiding processes of cell fate determination and organoid maturation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123349"},"PeriodicalIF":12.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-loaded antioxidant nanoplatforms for prevention and treatment of experimental acute and chronic uveitis","authors":"Siting Sheng ,&nbsp;Huiling Zhao ,&nbsp;Lirui Liu ,&nbsp;Dan Chen ,&nbsp;Xingdi Wu ,&nbsp;Chujun Liu ,&nbsp;Xinyu Ma ,&nbsp;Jing-Wei Xu ,&nbsp;Jian Ji ,&nbsp;Haijie Han ,&nbsp;Wen Xu","doi":"10.1016/j.biomaterials.2025.123353","DOIUrl":"10.1016/j.biomaterials.2025.123353","url":null,"abstract":"<div><div>Uveitis, a frequently recurrent inflammatory condition of the uvea, poses a significant risk of visual impairment and blindness, primarily due to the excessive generation of reactive oxygen species (ROS) and the activation of signaling pathways that propagate inflammatory responses. Despite the widespread use of corticosteroid eye drops as a standard treatment, these therapies are hindered by limited efficacy, adverse side effects, and poor ocular bioavailability. To address these challenges, polyethyleneimine (PEI)-modified polydopamine (PDA) carrying microRNA-132-3p (miR-132), namely PEI/PDA@miR-132, was developed to simultaneously neutralize ROS and attenuate inflammation in experimental models of acute and chronic uveitis. Mechanistically, PEI/PDA@miR-132 demonstrated remarkable efficacy by suppressing ROS production, inhibiting the pro-inflammatory polarization of macrophages, and downregulating the I<em>κ</em>B<em>α</em>/nuclear factor-kappa B (NF-<em>κ</em>B) p65 signaling pathway. These effects culminated in the reduction of pro-inflammatory cytokines and mitigation of apoptosis. Therapeutically, PEI/PDA@miR-132 provided significant relief from hallmark symptoms of uveitis, including iris congestion, inflammatory exudation, and retinal folds, while exhibiting superior retinal safety compared to commercially available dexamethasone. Furthermore, it showcased excellent biocompatibility, positioning it as a promising therapeutic strategy for managing oxidative stress- and inflammation-driven diseases such as acute and chronic uveitis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123353"},"PeriodicalIF":12.8,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanomotor-driven precision therapy for peritoneal metastasis","authors":"Yaoguang She ,&nbsp;Jianxin Cui ,&nbsp;Jiamin Ye ,&nbsp;Fei Pan ,&nbsp;Wenquan Liang ,&nbsp;Xiaofeng He ,&nbsp;Di Wu ,&nbsp;Xiaoyuan Ji ,&nbsp;Chunxi Wang","doi":"10.1016/j.biomaterials.2025.123354","DOIUrl":"10.1016/j.biomaterials.2025.123354","url":null,"abstract":"<div><div>Peritoneal metastasis (PM) is a terminal stage of gastrointestinal cancers, often resulting in poor survival outcomes. Traditional treatments like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown some effectiveness but are associated with significant risks. This study presents a novel nanomotor-based drug delivery system (M@MnO₂–Au-mSiO₂@CDDP) designed to enhance the efficacy of PM treatment. By utilizing an oxygen-driven heterojunction nanomotor (MnO₂–Au-mSiO₂), coated with membrane of M1-type macrophages, the system targets PM tumors with high precision through intraperitoneal perfusion. These biomimetic NMs promote deep tumor penetration, enhance reactive oxygen species (ROS) generation, and activate the STING pathway, a critical component in immune regulation. The catalytic properties of MnO₂ within the nanomotors enhance drug permeability and retention, enabling targeted and controlled drug release. Both in vitro and in vivo experiments demonstrated the system's ability to significantly inhibit tumor growth, induce apoptosis, and activate immune responses. In addition, the synergistic effect of targeted drug delivery, catalytic therapy and immunotherapy of this system was further confirmed by constructing an in vitro gastric cancer organoid model, showing great clinical application potential. The study also confirmed excellent biocompatibility and stability, making these NMs a promising clinical tool for the treatment of PM. This research underscores the potential of nanotechnology to revolutionize cancer treatment by overcoming the limitations of traditional therapies and paving the way for future innovations in targeted cancer therapies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123354"},"PeriodicalIF":12.8,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered bilayered grafts for structural and functional posterior lamellar eyelid reconstruction","authors":"Qiumei Ji ,&nbsp;Xingran Liu ,&nbsp;Ruize Tang ,&nbsp;Jing Yang ,&nbsp;Yan Zeng ,&nbsp;Rehanguli Aimaier ,&nbsp;Xiangqi Liu ,&nbsp;Valeriya V. Kardumyan ,&nbsp;Anna B. Solovieva ,&nbsp;Qingfeng Li ,&nbsp;Ru-Lin Huang","doi":"10.1016/j.biomaterials.2025.123351","DOIUrl":"10.1016/j.biomaterials.2025.123351","url":null,"abstract":"<div><div>Eyelid defects involving posterior lamella loss pose significant challenges in reconstructive surgery due to their functional-anatomical complexity. While our previous autologous auricular chondrocyte-derived tissue-engineered cartilage (TEC) grafts successfully maintained normal eyelid morphology, they lacked functional epithelium. This study develops bioengineered bilayered mucosa-cartilage (BMC) grafts through coculture of TEC with oral mucosal explants. The resulting BMC grafts demonstrated a stratified epithelium with barrier integrity and MUC1-producing capacity and a cartilage layer with surgical-grade tensile modulus (1.68 MPa). Upon transplantation into rabbit tarsoconjunctival defects, BMC grafts surpassed both untreated controls and TEC grafts. All grafts demonstrated integration by 2 weeks post-implantation, with transient inflammatory infiltration resolving by 8 weeks. BMC and TEC grafts better preserved eyelid morphology and blinking function than controls throughout the 8-week study. Crucially, BMC-reconstructed eyelids developed continuous stratified epithelia with 5.8-layer MUC1-secreting epithelial cells as early as 2 weeks, progressing to MUC5AC⁺ goblet cell-rich epithelia by 8 weeks post-implantation. In contrast, TEC counterparts formed thinner epithelia with a lower density of goblet cells. These results confirm the structural integrity and secretory functions of BMC grafts, advancing clinical translation of functional eyelid substitutes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123351"},"PeriodicalIF":12.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal structural characteristics of osteoinductivity in bioceramics derived from a novel high-throughput screening plus machine learning approach","authors":"Yunyi Liu ,&nbsp;Quanle Cao ,&nbsp;Shengyi Yong ,&nbsp;Jing Wang ,&nbsp;Xuening Chen ,&nbsp;Yumei Xiao ,&nbsp;Jiangli Lin ,&nbsp;Mingli Yang ,&nbsp;Kefeng Wang ,&nbsp;Xiangfeng Li ,&nbsp;Xiangdong Zhu ,&nbsp;Xingdong Zhang","doi":"10.1016/j.biomaterials.2025.123348","DOIUrl":"10.1016/j.biomaterials.2025.123348","url":null,"abstract":"<div><div>Osteoinduction is an important feature of the next generation of bone repair materials. But the key structural factors and parameters of osteoinductive scaffolds are not yet clarified. This study leverages the efficiency of high-throughput screening in identifying key structural factors, performs screening of 24 different porous structures using 3D printed calcium phosphate (CaP) ceramic scaffolds. Based on <em>in vitro</em> and <em>in vivo</em> evaluations, along with machine learning and nonlinear fitting, it explores the complex relationship between osteoinductive properties and scaffold configurations. Results indicate that bone regenerative ability is largely affected by porosity and specific surface area (SSA), while pore geometry has a negligible effect. The optimal structural parameters were identified as a porous structure with SSA of 10.49–10.69 mm² mm⁻³ and permeability of 3.74 × 10⁻⁹ m², which enhances osteoinductivity and scaffold properties, corresponding to approximately 65 %–70 % porosity. Moreover, nonlinear fitting reveals specific correlations among SSA, permeability and osteogenic gene expressions. We established a data-driven high-throughput screening methodology and proposed a parametric benchmark for osteoinductive structures, providing critical insights for the design of future osteoinductive scaffolds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123348"},"PeriodicalIF":12.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved immunocompatibility of active targeting liposomes by attenuating nucleophilic attack of cyclic RGD peptides on complement 3","authors":"Nana Meng ,&nbsp;Jiasheng Lu ,&nbsp;Jianfen Zhou ,&nbsp;Shengmin Yang ,&nbsp;Chen Zhang ,&nbsp;Ruiyi Jia ,&nbsp;Yuan Ding ,&nbsp;Yanning Bao ,&nbsp;Jun Wang ,&nbsp;Xiaopei Ma ,&nbsp;Ruohan Chen ,&nbsp;Zhixuan Jiang ,&nbsp;Cao Xie ,&nbsp;Linwei Lu ,&nbsp;Weiyue Lu","doi":"10.1016/j.biomaterials.2025.123350","DOIUrl":"10.1016/j.biomaterials.2025.123350","url":null,"abstract":"<div><div>One of the challenges for the clinical translation of active targeting nanomedicines is the adverse interactions between targeting ligands and blood components. Herein, a novel regularity, which reveals the interactions between cyclic RGD (Arg-Gly-Asp) peptide-modified liposomes and complement components in blood, is reported. As the nucleophilicity of arginine guanidine group within the cyclic RGD-like peptide increases, targeting liposomes potentiate complement cascade via the amplification loop of complement 3 (C3), ultimately leading to accelerated blood clearance, increased deposition in the reticuloendothelial system (RES) organs, enhanced immune responses, and potential side effects. By appropriately reducing the nucleophilicity of guanidine group, cyclic R2 peptide is designed for modification of liposomes to target integrin <em>α</em>_<em>v</em><em>β</em>_<em>3</em>. Compared to the widely used targeting molecule c(RGDyK), R2 eliminates the negative effects of C3 opsonization and specific antibody production, significantly improves the <em>in vivo</em> immunocompatibility of targeting liposomes, and demonstrates superior anti-tumor efficacy in mouse models of orthotopic breast cancer and glioma. Thus, the proposed regularity of interactions between guanidine nucleophilicity and C3, along with the successful application of the low complement activation capacity targeting ligand R2, provides new insights for addressing challenges related to complement activation in the clinical translation of active targeting nanomedicines.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123350"},"PeriodicalIF":12.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone marrow adipocytes in cancer: Mechanisms, models, and therapeutic implications","authors":"Agathe Bessot ,&nbsp;Jennifer Gunter ,&nbsp;Jacqui McGovern ,&nbsp;Nathalie Bock","doi":"10.1016/j.biomaterials.2025.123341","DOIUrl":"10.1016/j.biomaterials.2025.123341","url":null,"abstract":"<div><div>Adipose tissue is the primary site of energy storage in the body and a key regulator of metabolism. However, different adipose depots exhibit distinct molecular and phenotypic characteristics that have yet to be fully unraveled. While initially considered inert, bone marrow adipocytes (BMAs) have been recognized as key regulators of bone homeostasis, and more recently bone pathologies, although many unknowns remain. In this review, we summarize the current knowledge on BMAs, focusing on their distinct characteristics, functional significance in bone physiology and metabolism, as well as their emerging role in cancer pathogenesis. We present and discuss the current methodologies for investigating BMA-cancer interactions, encompassing both <em>in vitro</em> 3D culture systems and <em>in vivo</em> models, and their limitations in accurately replicating the phenotypes and biological processes of the human species. We highlight the imperative for advancing towards humanized models to better mimic the complexities of human physiology and disease progression. Finally, therapeutic strategies targeting metabolism or BMA-secreted factors, such as anti-cholesterol drugs, hold considerable promise in cancer treatment. We present the synergistic avenue of combining conventional cancer therapies with agents targeting adipocyte signaling to amplify treatment efficacy. Developing preclinical models that more faithfully replicate human pathological and physiological processes will lead to more accurate mechanistic understanding of the role of BMAs in bone metastasis and lead to more relevant preclinical drug screening.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123341"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative sarcoma therapy using multifaceted nano-PROTAC-induced EZH2 degradation and immunity enhancement","authors":"Zhihao Chen ,&nbsp;Yi Tai ,&nbsp;Chuangzhong Deng ,&nbsp;Yameng Sun ,&nbsp;Hongmin Chen ,&nbsp;Tianqi Luo ,&nbsp;Jiaming Lin ,&nbsp;Weiqing Chen ,&nbsp;Huaiyuan Xu ,&nbsp;Guohui Song ,&nbsp;Qinglian Tang ,&nbsp;Jinchang Lu ,&nbsp;Xiaojun Zhu ,&nbsp;Shijun Wen ,&nbsp;Jin Wang","doi":"10.1016/j.biomaterials.2025.123344","DOIUrl":"10.1016/j.biomaterials.2025.123344","url":null,"abstract":"<div><div>Sarcomas are highly malignant tumors characterized by their heterogeneity and resistance to conventional therapies, which significantly limit treatment options. EZH2 is highly expressed in sarcomas, but targeting it is difficult. In this study, we uncovered the non-canonical transcriptional mechanisms of EZH2 in sarcoma and highlighted the essential role of EZH2 in regulating YAP1 through non-canonical transcriptional pathways in the progression of sarcoma. Building on this, we developed YM@VBM, a novel and versatile nano-PROTAC (proteolysis-targeting chimera), by integrating a polyphenol-vanadium oxide system with the EZH2 degrader YM281 PROTAC, encapsulated in methoxy polyethylene glycol-NH₂ to enhance biocompatibility. To further facilitate targeted drug delivery to tumors, YM@VBM nano-PROTACs were incorporated into microneedle patches. Our engineered YM@VBM exhibited multiple functionalities, including the peroxidase-like activity to generate reactive oxygen species, depletion of glutathione, and photothermal effects, specifically targeting sarcoma characteristics. YM@VBM significantly enhanced targeting efficacy via inducing potent EZH2 degradation. Most importantly, it can also activate anti-tumor immunity via excluding myeloid-derived suppressor cells, maturing dendritic cells, and forming tertiary lymphoid structures. Hence, we reveal that YM@VBM presents a promising treatment strategy for sarcoma, offering a multifaceted approach to combat this challenging malignancy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123344"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}