Biomaterials最新文献

Smearable CQD-entrapped hydrogel with sensitive pH response and photodynamic antibacterial properties for visual intelligent wound monitoring

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-23 DOI: 10.1016/j.biomaterials.2025.123360

Yun Yuan , Zirong Li , Leilei Wu , Xinyi Cheng , Chao Deng , Yuanyuan Yu , Qiang Wang , Ping Wang

{"title":"Smearable CQD-entrapped hydrogel with sensitive pH response and photodynamic antibacterial properties for visual intelligent wound monitoring","authors":"Yun Yuan , Zirong Li , Leilei Wu , Xinyi Cheng , Chao Deng , Yuanyuan Yu , Qiang Wang , Ping Wang","doi":"10.1016/j.biomaterials.2025.123360","DOIUrl":"10.1016/j.biomaterials.2025.123360","url":null,"abstract":"<div><div>The treatment of chronic wounds remains a significant challenge in the clinical field, and optimizing the treatment plan through visual monitoring of wound healing is an effective way to solve such problem. Herein, we propose a feasible strategy to construct a smearable C–P-T/mCQDs hydrogel for real-time monitoring of wound infection and healing status, through the synergistic combination of modified carbon quantum dots (mCQD), cellulose nanofiber, tannic acid, and polyvinyl alcohol. The hydrogel can be readily applied on the skin and rapidly forms a gel dressing through high-density hydrogen bonding, demonstrating exceptional mechanical robustness (tensile elongation: 600 %) and autonomous self-healing capabilities. In particular, the carboxyl-rich mCQDs are more easily recognized by the sensitive pH-mediated polychromatic fluorescence response under ultraviolet excitation, exhibiting encouraging photodynamic therapy effect against bacterial infections. Under the irradiation of sunlight or near-infrared laser, the hydrogel achieves 99.99 % bactericidal efficacy against multiple types of bacteria (<em>S. aureus, E. coli, P. aeruginosa, A. baumannii</em>) within 20 min through reactive oxygen species generation. Furthermore, C–P-T/mCQDs demonstrates excellent antioxidant activity, biocompatibility, hemostatic efficiency and pro-healing properties. Notably, the mCQD-integrated hydrogel enables real-time, visual monitoring of wound status through its pH-responsive properties, providing substantial translational potential for personalized chronic wound management.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123360"},"PeriodicalIF":12.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873558","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}

引用次数: 0

Manganese-based nanoadjuvants for the synergistic enhancement of immune responses in breast cancer therapy via disulfidptosis-induced ICD and cGAS-STING activation

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-22 DOI: 10.1016/j.biomaterials.2025.123359

Ke Zhang, Chengyao Huang, Yu Ren, Mingyue Zhang, Xiaotong Lu, Bangliu Yang, Peiran Chen, Shiyao Guo, Xueqian Wang, Yuhong Zhuo, Chao Qi, Kaiyong Cai

{"title":"Manganese-based nanoadjuvants for the synergistic enhancement of immune responses in breast cancer therapy via disulfidptosis-induced ICD and cGAS-STING activation","authors":"Ke Zhang, Chengyao Huang, Yu Ren, Mingyue Zhang, Xiaotong Lu, Bangliu Yang, Peiran Chen, Shiyao Guo, Xueqian Wang, Yuhong Zhuo, Chao Qi, Kaiyong Cai","doi":"10.1016/j.biomaterials.2025.123359","DOIUrl":"10.1016/j.biomaterials.2025.123359","url":null,"abstract":"<div><div>Tumor immunotherapy represents one of the most promising strategies for combating tumors by activating the immune system, harnessing anti-tumor immune cells to eliminate tumor cells, and preventing tumor recurrence and metastasis. However, clinical data indicate that the anti-tumor immune response is often inadequate in many cancer patients, resulting in the failure of tumor immunotherapy. Herein, we report a manganese (Mn)-based nanoadjuvant (denoted as BMP-Au) aimed at synergistically enhancing anti-tumor immune responses in breast cancer therapy through disulfidptosis-induced immunogenic cell death and Mn-mediated cGAS-STING pathway activation. BMP-Au is synthesized using bovine serum albumin as a biotemplate for biomimetic mineralization of manganese phosphate nanosheets, followed by the deposition of gold nanoparticles (Au NPs) on their surface. By exploiting the glucose oxidase-like activity of Au NPs alongside the Fenton-like reaction facilitated by Mn<sup>2+</sup>, BMP-Au orchestrates a cascade catalytic reaction that generates reactive oxygen species from glucose. This process not only initiates disulfidptosis but also leads to DNA fragmentation crucial for activating the cGAS-STING pathway. These concurrent mechanisms compromise cancer cell viability while significantly enhancing tumor immunogenicity, positioning BMP-Au as an innovative nanoadjuvant for cancer treatment that leverages both cellular stress mechanisms and immune activation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123359"},"PeriodicalIF":12.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876939","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}

引用次数: 0

Transforming malignant tumors into vulnerable phenotypes via nanoscale coordination polymer mediated cell senescence and photodynamic therapy

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-22 DOI: 10.1016/j.biomaterials.2025.123355

Wenyao Zhen , Xiaomin Jiang , En Li , Tomas Germanas , Morten J. Lee , Taokun Luo , Xin Ma , Chaoyu Wang , Yimei Chen , Ralph R. Weichselbaum , Wenbin Lin

{"title":"Transforming malignant tumors into vulnerable phenotypes via nanoscale coordination polymer mediated cell senescence and photodynamic therapy","authors":"Wenyao Zhen , Xiaomin Jiang , En Li , Tomas Germanas , Morten J. Lee , Taokun Luo , Xin Ma , Chaoyu Wang , Yimei Chen , Ralph R. Weichselbaum , 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}

引用次数: 0

Tumor-specific activated polymeric nanotuners disrupt positive feedback cycle of hypoxia and apoptosis evasion for potent cancer radiotherapy

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-22 DOI: 10.1016/j.biomaterials.2025.123361

Xiaoxue Hou , Chun Wang , Yu Zhao , Qian Wang , Dianyu Wang , Jingyu Zhao , Yang Liu , Fan Huang , Jianfeng Liu

{"title":"Tumor-specific activated polymeric nanotuners disrupt positive feedback cycle of hypoxia and apoptosis evasion for potent cancer radiotherapy","authors":"Xiaoxue Hou , Chun Wang , Yu Zhao , Qian Wang , Dianyu Wang , Jingyu Zhao , Yang Liu , Fan Huang , 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 (H<sub>2</sub>O<sub>2</sub>) into oxygen (O<sub>2</sub>) 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}

引用次数: 0

MicroRNA-loaded antioxidant nanoplatforms for prevention and treatment of experimental acute and chronic uveitis

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-20 DOI: 10.1016/j.biomaterials.2025.123353

Siting Sheng , Huiling Zhao , Lirui Liu , Dan Chen , Xingdi Wu , Chujun Liu , Xinyu Ma , Jing-Wei Xu , Jian Ji , Haijie Han , Wen Xu

{"title":"MicroRNA-loaded antioxidant nanoplatforms for prevention and treatment of experimental acute and chronic uveitis","authors":"Siting Sheng , Huiling Zhao , Lirui Liu , Dan Chen , Xingdi Wu , Chujun Liu , Xinyu Ma , Jing-Wei Xu , Jian Ji , Haijie Han , 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}

引用次数: 0

Nanomotor-driven precision therapy for peritoneal metastasis

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-20 DOI: 10.1016/j.biomaterials.2025.123354

Yaoguang She , Jianxin Cui , Jiamin Ye , Fei Pan , Wenquan Liang , Xiaofeng He , Di Wu , Xiaoyuan Ji , Chunxi Wang

{"title":"Nanomotor-driven precision therapy for peritoneal metastasis","authors":"Yaoguang She , Jianxin Cui , Jiamin Ye , Fei Pan , Wenquan Liang , Xiaofeng He , Di Wu , Xiaoyuan Ji , 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@MnO<sub>2</sub>–Au-mSiO<sub>2</sub>@CDDP) designed to enhance the efficacy of PM treatment. By utilizing an oxygen-driven heterojunction nanomotor (MnO<sub>2</sub>–Au-mSiO<sub>2</sub>), 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 MnO<sub>2</sub> 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}

引用次数: 0

Bioengineered bilayered grafts for structural and functional posterior lamellar eyelid reconstruction

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-17 DOI: 10.1016/j.biomaterials.2025.123351

Qiumei Ji , Xingran Liu , Ruize Tang , Jing Yang , Yan Zeng , Rehanguli Aimaier , Xiangqi Liu , Valeriya V. Kardumyan , Anna B. Solovieva , Qingfeng Li , Ru-Lin Huang

{"title":"Bioengineered bilayered grafts for structural and functional posterior lamellar eyelid reconstruction","authors":"Qiumei Ji , Xingran Liu , Ruize Tang , Jing Yang , Yan Zeng , Rehanguli Aimaier , Xiangqi Liu , Valeriya V. Kardumyan , Anna B. Solovieva , Qingfeng Li , 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<sup>+</sup> 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}

引用次数: 0

Optimal structural characteristics of osteoinductivity in bioceramics derived from a novel high-throughput screening plus machine learning approach

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-16 DOI: 10.1016/j.biomaterials.2025.123348

Yunyi Liu , Quanle Cao , Shengyi Yong , Jing Wang , Xuening Chen , Yumei Xiao , Jiangli Lin , Mingli Yang , Kefeng Wang , Xiangfeng Li , Xiangdong Zhu , Xingdong Zhang

{"title":"Optimal structural characteristics of osteoinductivity in bioceramics derived from a novel high-throughput screening plus machine learning approach","authors":"Yunyi Liu , Quanle Cao , Shengyi Yong , Jing Wang , Xuening Chen , Yumei Xiao , Jiangli Lin , Mingli Yang , Kefeng Wang , Xiangfeng Li , Xiangdong Zhu , 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 mm<sup>2</sup> mm<sup>−3</sup> and permeability of 3.74 × 10<sup>−9</sup> m<sup>2</sup>, 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}

引用次数: 0

Improved immunocompatibility of active targeting liposomes by attenuating nucleophilic attack of cyclic RGD peptides on complement 3 通过减弱环状 RGD 肽对补体 3 的亲核攻击，提高活性靶向脂质体的免疫相容性

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-16 DOI: 10.1016/j.biomaterials.2025.123350

Nana Meng , Jiasheng Lu , Jianfen Zhou , Shengmin Yang , Chen Zhang , Ruiyi Jia , Yuan Ding , Yanning Bao , Jun Wang , Xiaopei Ma , Ruohan Chen , Zhixuan Jiang , Cao Xie , Linwei Lu , Weiyue Lu

{"title":"Improved immunocompatibility of active targeting liposomes by attenuating nucleophilic attack of cyclic RGD peptides on complement 3","authors":"Nana Meng , Jiasheng Lu , Jianfen Zhou , Shengmin Yang , Chen Zhang , Ruiyi Jia , Yuan Ding , Yanning Bao , Jun Wang , Xiaopei Ma , Ruohan Chen , Zhixuan Jiang , Cao Xie , Linwei Lu , 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><sub><em>v</em></sub><em>β</em><sub><em>3</em></sub>. 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}

引用次数: 0

Innovative sarcoma therapy using multifaceted nano-PROTAC-induced EZH2 degradation and immunity enhancement

IF 12.8 1区医学

Biomaterials Pub Date : 2025-04-15 DOI: 10.1016/j.biomaterials.2025.123344

Zhihao Chen , Yi Tai , Chuangzhong Deng , Yameng Sun , Hongmin Chen , Tianqi Luo , Jiaming Lin , Weiqing Chen , Huaiyuan Xu , Guohui Song , Qinglian Tang , Jinchang Lu , Xiaojun Zhu , Shijun Wen , Jin Wang

{"title":"Innovative sarcoma therapy using multifaceted nano-PROTAC-induced EZH2 degradation and immunity enhancement","authors":"Zhihao Chen , Yi Tai , Chuangzhong Deng , Yameng Sun , Hongmin Chen , Tianqi Luo , Jiaming Lin , Weiqing Chen , Huaiyuan Xu , Guohui Song , Qinglian Tang , Jinchang Lu , Xiaojun Zhu , Shijun Wen , 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-NH<sub>2</sub> 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}

引用次数: 0