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Magnesium peroxide-based biomimetic nanoigniter degrades extracellular matrix to awake T cell-mediated cancer immunotherapy.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-27 DOI: 10.1016/j.biomaterials.2024.123043
Huisong Hao, Shengjie Sun, Yanan Fu, Simin Wen, Yingfei Wen, Yunfei Yi, Zhangwen Peng, Yixuan Fang, Jia Tang, Tianqi Wang, Meiying Wu
{"title":"Magnesium peroxide-based biomimetic nanoigniter degrades extracellular matrix to awake T cell-mediated cancer immunotherapy.","authors":"Huisong Hao, Shengjie Sun, Yanan Fu, Simin Wen, Yingfei Wen, Yunfei Yi, Zhangwen Peng, Yixuan Fang, Jia Tang, Tianqi Wang, Meiying Wu","doi":"10.1016/j.biomaterials.2024.123043","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123043","url":null,"abstract":"<p><p>As the elite force of our immune system, T cells play a determining role in the effectiveness of cancer immunotherapy. However, the clever tumor cells construct a strong immunosuppressive tumor microenvironment (TME) fortress to resist the attack of T cells. Herein, a magnesium peroxide (MP)-based biomimetic nanoigniter loaded with doxorubicin (DOX) and metformin (MET) is rationally designed (D/M-MP@LM) to awake T cell-mediated cancer immunotherapy via comprehensively destroying the strong TME fortress. The nanoigniter not only effectively initiate CD8<sup>+</sup> T cell-mediated immune response by promoting the presentation of tumor antigens, but also greatly facilitate the infiltration of T cells by degrading rigid extracellular matrix (ECM). More importantly, the nanoigniter significantly augment the effector functions of infiltrated CD8<sup>+</sup> T cells by Mg<sup>2+</sup>-mediated metalloimmunotherapy and avoid the exhaustion of CD8<sup>+</sup> T cells by improving the acidic TME. Thus, the nanoigniter comprehensively awakes T cells and achieves remarkable tumor inhibition efficacy.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123043"},"PeriodicalIF":12.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925857","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
Black phosphorus nanosheets activate tumor immunity of glioblastoma by modulating the expression of the immunosuppressive molecule PD-L1. 黑磷纳米片通过调节免疫抑制分子 PD-L1 的表达激活胶质母细胞瘤的肿瘤免疫力
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-27 DOI: 10.1016/j.biomaterials.2024.123062
Yue Xiong, Chao He, Junyang Qi, Meimei Xiong, Shuna Liu, Jingxin Zhao, Yuzhen Li, Gan Liu, Wenbin Deng
{"title":"Black phosphorus nanosheets activate tumor immunity of glioblastoma by modulating the expression of the immunosuppressive molecule PD-L1.","authors":"Yue Xiong, Chao He, Junyang Qi, Meimei Xiong, Shuna Liu, Jingxin Zhao, Yuzhen Li, Gan Liu, Wenbin Deng","doi":"10.1016/j.biomaterials.2024.123062","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123062","url":null,"abstract":"<p><p>The tumor microenvironment in glioblastoma (GBM) is characterized by a pronounced immunosuppressive state, which significantly hampers tumor treatment and contributes to treatment resistance. While our previous research established that black phosphorus nanosheets (BPNS) inhibited glioblastoma cell migration and invasion, the impact of BPNS on the anti-tumor-associated immune mechanism remains unexplored. This study firstly investigated whether BPNS could modulate the tumor microenvironment through immunotherapy and elucidated the underlying mechanisms. We used a subcutaneous mouse model of GBM, which evaded immune surveillance to evaluate BPNS effects on immune cells within the tumor microenvironment. Our results demonstrated that BPNS significantly enhanced the tumor-suppressive microenvironment, reactivating immune cells' cytotoxicity against tumor cells. Moreover, further analysis revealed that BPNS counteracted the immunosuppressive state by reducing the expression of the immunosuppressive molecule PD-L1 in tumor cells, leading to an anti-tumor effect. Mechanistically, BPNS reduced PD-L1 expression through two main pathways: by inducing autophagy via binding to the HSP90 protein, leading to PD-L1 degradation through the autophagy pathway, and by inhibiting the PI3K-AKT signaling pathway, which reduced PD-L1 mRNA levels. This study expands the understanding of BPNS biological activity and suggests new strategies for utilizing BPNS as an adjuvant in immunotherapy.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123062"},"PeriodicalIF":12.8,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906409","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
Injectable bioresponsive bone adhesive hydrogels inhibit NLRP3 inflammasome on demand to accelerate diabetic fracture healing.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-26 DOI: 10.1016/j.biomaterials.2024.123059
Xudan Xing, Zunlei Gong, Chuke Chen, Yeyin Lin, Peiyi Liu, Tianhua Xiao, Hui Yu, Yuanxin Li, Yucong Lin, Guoxin Tan, Chengyun Ning, Zenghui Wu, Le Wang, Lei Zhou
{"title":"Injectable bioresponsive bone adhesive hydrogels inhibit NLRP3 inflammasome on demand to accelerate diabetic fracture healing.","authors":"Xudan Xing, Zunlei Gong, Chuke Chen, Yeyin Lin, Peiyi Liu, Tianhua Xiao, Hui Yu, Yuanxin Li, Yucong Lin, Guoxin Tan, Chengyun Ning, Zenghui Wu, Le Wang, Lei Zhou","doi":"10.1016/j.biomaterials.2024.123059","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123059","url":null,"abstract":"<p><p>Diabetes is associated with excessive inflammation, which negatively impacts the fracture healing process and delays bone repair. Previously, growing evidence indicated that activation of the nod-like receptor (NLR) family, such as nod-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome induces a vicious cycle of chronic low-grade inflammatory responses in diabetic fracture. Here, we describe the synthesis of a bone adhesive hydrogel that can be locally injected into the fracture site and releases a natural inhibitor of NLRP3 (rutin) in response to pathological cue reactive oxygen species activity (ROS). The hydrogel (denoted as RPO) was facilely formed by the cross-linking of rutin-functionalized gelatin, poly(vinyl alcohol), and oxidized starch based on the dynamic schiff base and boronate ester bond. Specifically, rutin is conjugated in the RPO hydrogel via a ROS linker and is released as the linker is cleaved by active ROS. In vitro studies demonstrate that RPO hydrogel effectively mitigates oxidative stress, alleviates mitochondrial dysfunction, and limits the overactivation of NLRP3 inflammasome in bone marrow derived macrophages, thereby promoting osteogenic differentiation of bone marrow mesenchymal stem cells. In a diabetic rat fracture model, RPO hydrogel significantly accelerates bone repair by modulating the inflammatory microenvironment. Our results demonstrate that local, on-demand NLRP3 inhibition for the treatment of diabetic fracture is achievable by using an injectable bioresponsive adhesive RPO hydrogel.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123059"},"PeriodicalIF":12.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890809","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
Janus PEGylated CuS-engineered Lactobacillus casei combats biofilm infections via metabolic interference and innate immunomodulation.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-26 DOI: 10.1016/j.biomaterials.2024.123060
Lingtong Kong, Xianli Hu, Demeng Xia, Jianghong Wu, Yangpeng Zhao, Hua Guo, Song Zhang, Chun Qin, Yanjun Wang, Lei Li, Zheng Su, Chen Zhu, Shuogui Xu
{"title":"Janus PEGylated CuS-engineered Lactobacillus casei combats biofilm infections via metabolic interference and innate immunomodulation.","authors":"Lingtong Kong, Xianli Hu, Demeng Xia, Jianghong Wu, Yangpeng Zhao, Hua Guo, Song Zhang, Chun Qin, Yanjun Wang, Lei Li, Zheng Su, Chen Zhu, Shuogui Xu","doi":"10.1016/j.biomaterials.2024.123060","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123060","url":null,"abstract":"<p><p>Bacterial implant-associated infections predominantly contribute to the failure of prosthesis implantation. The local biofilm microenvironment (BME), characterized by its hyperacidic condition and high hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) level, inhibits the host's immune response, thereby facilitating recurrent infections. Here, a Janus PEGylated CuS nanoparticle (CuPen) armed engineered Lactobacillus casei (L. casei) denoted as LC@CuPen, is proposed to interfere with bacterial metabolism and arouse macrophage antibiofilm function. Once LC@CuPen reached the BME, NIR irradiation-activated mild heat damages L. casei and biofilm structure. Meanwhile, the BME-responsive LC@CuPen can catalyze local H<sub>2</sub>O<sub>2</sub> to produce toxic •OH, whereas in normal tissues, the effect of •OH production is greatly reduced due to the higher pH and lower H<sub>2</sub>O<sub>2</sub> concentration. The released bacteriocin from damaged L. casei can destroy the bacterial membrane to enhance the penetration of •OH into damaged biofilm. Excessive •OH interferes with normal bacterial metabolism, resulting in reduced resistance of bacteria to heat stress. Finally, under the action of mild heat treatment, the bacterial biofilm lysed and died. Furthermore, the pathogen-associated molecular patterns (PAMPs) in LC@CuPen can induce M1 polarization of macrophages through NF-κB pathway and promote the release of inflammatory factors. Inflammatory factors enhance the migration of macrophages to the site of infection and phagocytose bacteria, thereby inhibiting the recurrence of infection. Generally, this engineered L. casei program presents a novel perspective for the treatment of bacterial implant-associated infections and serves as a valuable reference for future clinical applications of engineered probiotics.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123060"},"PeriodicalIF":12.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906412","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
Phycocyanin-based multifunctional microspheres for treatment of infected radiation-induced skin injury.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-26 DOI: 10.1016/j.biomaterials.2024.123061
Jia Dong, Yutong Lang, Jian He, Jiarong Cui, Xiaoyang Liu, Hongxia Yuan, Lele Li, Min Zhou, Shoujie Wang
{"title":"Phycocyanin-based multifunctional microspheres for treatment of infected radiation-induced skin injury.","authors":"Jia Dong, Yutong Lang, Jian He, Jiarong Cui, Xiaoyang Liu, Hongxia Yuan, Lele Li, Min Zhou, Shoujie Wang","doi":"10.1016/j.biomaterials.2024.123061","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123061","url":null,"abstract":"<p><p>Radiation therapy is a primary modality for cancer treatment; however, it often leads to various degrees of skin injuries, ranging from mild rashes to severe ulcerations, for which no effective treatments are currently available. In this study, a multifunctional microsphere (PC@CuS-ALG) was synthesized by encapsulating phycocyanin-templated copper sulfide nanoparticles (PC@CuS) within alginate (ALG) using microfluidic technology. Phycocyanin, a natural protein derived from microalgae, shows abilities to scavenge reactive oxygen species, repair radiation-induced damage to skin cells, and ameliorate macrophage-related inflammatory responses. CuS contributes to photothermal conversion efficiency and exhibits antibacterial properties. The microspheres facilitate the sustained release of PC@CuS, retain moisture at the wound site, and provide a supportive environment for cell migration and growth. In a mouse model of infected radiation-induced skin injury, PC@CuS-ALG exhibited antibacterial and wound healing effects, resulting in accelerated epidermal tissue regeneration, increased thickness and maturation of dermal granulation tissue, and an ameliorated inflammatory response. This study presents a novel, effective, and safe approach for treating radiation-induced skin injuries complicated by bacterial infection.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123061"},"PeriodicalIF":12.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913446","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
Bioactive microspheres to enhance sonodynamic-embolization-metalloimmune therapy for orthotopic liver cancer.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-26 DOI: 10.1016/j.biomaterials.2024.123063
Jiachen Xu, Zifan Pei, Yuanjie Wang, Nan Jiang, Yuehan Gong, Fei Gong, Caifang Ni, Liang Cheng
{"title":"Bioactive microspheres to enhance sonodynamic-embolization-metalloimmune therapy for orthotopic liver cancer.","authors":"Jiachen Xu, Zifan Pei, Yuanjie Wang, Nan Jiang, Yuehan Gong, Fei Gong, Caifang Ni, Liang Cheng","doi":"10.1016/j.biomaterials.2024.123063","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123063","url":null,"abstract":"<p><p>The development of novel microspheres for the combination of sonodynamic therapy (SDT) with transarterial embolization (TAE) therapy to amplify their efficacy has received increasing attention. Herein, a novel strategy for encapsulating sonosensitizers (e.g., oxygen-deficient manganese tungstate (MnWO<sub>X</sub>) nanodots) with gelatin microspheres was proposed. The obtained MnWO<sub>X</sub>-encapsulated microspheres (abbr. Mn-GMSs) facilitated efficient sonodynamic-embolization-metalloimmune therapy via the immune effects of metal ions on orthotopic liver cancer tumor after transarterial embolization (TAE). Due to the strong cavitation effect caused by the porous structure, Mn-GMSs exhibited a greater reactive oxygen species (ROS) generation rate than the free MnWO<sub>X</sub> nanodots under US irradiation. Efficient SDT revealed robust cell-killing effects and triggered strong immunogenic cell death (ICD). Moreover, the Mn ions released from the bioactive Mn-GMSs further stimulated the dendritic cells (DCs) maturation and triggered the activation of the cGAS/STING pathway to enhance the immunological effect. Thus, Mn-GMSs achieved significant SDT therapeutic outcomes in H22 tumors in mice, and the combination of the Mn-GMSs triggered SDT with programmed cell death ligand 1 (PD-L1) antibodies could further enhance therapeutic outcomes. The Mn-GMSs exhibited high ROS generation efficacy under US irradiation, significant immune activation, good efficacy in combination with immune checkpoint inhibitor, and great potential for artery embolization-assisted drug delivery, thus enabling effective destruction of liver tumors in rats and rabbits. Therefore, this work provides a strategy for applying SDT in deep tumors and highlights a promising sonodynamic-embolization therapy for combating liver cancers.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123063"},"PeriodicalIF":12.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925845","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
Hydrogel injection molded complex macroencapsulation device geometry improves long-term cell therapy viability and function in the rat omentum transplant site.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-26 DOI: 10.1016/j.biomaterials.2024.123040
Amy E Emerson, Quincy Lyons, Matthew W Becker, Keven Sepulveda, Shivani C Hiremath, Sarah R Brady, Chishiba Chilimba, Jessica D Weaver
{"title":"Hydrogel injection molded complex macroencapsulation device geometry improves long-term cell therapy viability and function in the rat omentum transplant site.","authors":"Amy E Emerson, Quincy Lyons, Matthew W Becker, Keven Sepulveda, Shivani C Hiremath, Sarah R Brady, Chishiba Chilimba, Jessica D Weaver","doi":"10.1016/j.biomaterials.2024.123040","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123040","url":null,"abstract":"<p><p>Insulin-secreting allogeneic cell therapies are a promising treatment for type 1 diabetes, with the potential to eliminate hypoglycemia and long-term complications of the disease. However, chronic systemic immunosuppression is necessary to prevent graft rejection, and the acute risks associated with immunosuppression limit the number of patients who can be treated with allogeneic cell therapies. Islet macroencapsulation in a hydrogel biomaterial is one proposed method to reduce or eliminate immune suppression; however, macroencapsulation devices suffer from poor oxygen transport and limited efficacy as they scale to large animal model preclinical studies and clinical trials. Hydrogel geometric device designs that optimize nutrient transport combined with methods to promote localized vasculogenesis may improve in vivo macroencapsulated cell viability and function. Here, we demonstrate with finite element modeling that a high surface area-to-volume ratio spiral geometry can increase macroencapsulated islet viability and function relative to a traditional cylindrical design, and we validate these observations in vitro under normoxic and physiological oxygen conditions. Finally, we evaluate macroencapsulated syngeneic islet survival and function in vivo in a diabetic rat omentum transplant model, and demonstrate that high surface area-to-volume hydrogel device designs improved macroencapsulated syngeneic islet function relative to traditional device designs.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123040"},"PeriodicalIF":12.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925849","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
Transduction enhancing EF-C peptide nanofibrils are endocytosed by macropinocytosis and subsequently degraded.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-25 DOI: 10.1016/j.biomaterials.2024.123044
Lena Rauch-Wirth, Desiree Schütz, Rüdiger Groß, Sascha Rode, Bernhard Glocker, Janis A Müller, Paul Walther, Clarissa Read, Jan Münch
{"title":"Transduction enhancing EF-C peptide nanofibrils are endocytosed by macropinocytosis and subsequently degraded.","authors":"Lena Rauch-Wirth, Desiree Schütz, Rüdiger Groß, Sascha Rode, Bernhard Glocker, Janis A Müller, Paul Walther, Clarissa Read, Jan Münch","doi":"10.1016/j.biomaterials.2024.123044","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123044","url":null,"abstract":"<p><p>Retroviral gene transfer is the preferred method for stable, long-term integration of genetic material into cellular genomes, commonly used to generate chimeric antigen receptor (CAR)-T cells designed to target tumor antigens. However, the efficiency of retroviral gene transfer is often limited by low transduction rates due to low vector titers and electrostatic repulsion between viral particles and cellular membranes. To overcome these limitations, peptide nanofibrils (PNFs) can be applied as transduction enhancers. Among these, PNFs derived from the 12-mer peptide EF-C are well-investigated and commercially available. EF-C PNFs enhance transduction by forming EF-C PNFs/virus complexes that overcome electrostatic repulsion through their polycationic surface and interaction with cellular protrusions. However, the safe application of PNFs as transduction enhancers in gene therapeutic applications requires a fundamental understanding of their transduction-enhancing mechanisms, uptake, and degradation. In this study, we demonstrate that EF-C PNFs induce plasma membrane invaginations, increasing the membrane surface for viral attachment and reducing the distance to the nuclear membrane, thereby facilitating viral entry and transport to the nucleus. Furthermore, we identified macropinocytosis as the main entry pathway for EF-C PNFs and their subsequent degradation by lysosomal peptidases. The lysosomal degradation of EF-C PNFs prevents their accumulation as amyloid deposits, mitigating potential side effects and supporting their safe use in clinical applications.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123044"},"PeriodicalIF":12.8,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925860","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
Hybrid membrane based biomimetic nanodrug with high-efficient melanoma-homing and NIR-II laser-amplified peroxynitrite boost properties for enhancing antitumor therapy via effective immunoactivation.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-24 DOI: 10.1016/j.biomaterials.2024.123045
Qi Lin, Yu Zhang, Yina Zeng, Yongchao Zha, Wei Xue, Siming Yu
{"title":"Hybrid membrane based biomimetic nanodrug with high-efficient melanoma-homing and NIR-II laser-amplified peroxynitrite boost properties for enhancing antitumor therapy via effective immunoactivation.","authors":"Qi Lin, Yu Zhang, Yina Zeng, Yongchao Zha, Wei Xue, Siming Yu","doi":"10.1016/j.biomaterials.2024.123045","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123045","url":null,"abstract":"<p><p>Owing to the excellent stability, anticancer activity and immunogenicity, peroxynitrite (ONOO<sup>-</sup>) has been gained enormous interests in cancer therapy. Nevertheless, precise delivery and control release of ONOO<sup>-</sup> in tumors remains a big challenge. Herein, B16F10 cancer cell membrane/liposome hybrid membrane (CM-Lip) based biomimetic nanodrug with high-efficient tumor-homing and NIR-II laser controlled ONOO<sup>-</sup> boost properties was designed for melanoma treatment. Briefly, NIR-II molecule IR1061, NO donor BNN6 and β-lapachone (Lapa) were firstly encapsulated in the heat-responsive palmitoyl phosphatidylcholine/cholesterol liposome, followed by fusion with B16F10 cell membrane (CM) to obtain biomimetic CM-Lip@(IR/BNN6/Lapa). The hybrid membrane-based nanodrug displayed excellent biocompatibility and melanoma-targeting efficiency. Upon 1064 nm laser irradiation, the mild photothermal effect of CM-Lip@(IR/BNN6/Lapa) firstly triggered the release of NO and Lapa, which subsequently catalyzed the quinone oxidoreductase 1 (NQO1) overexpressed in tumors to produce O<sub>2</sub><sup>•-</sup>, finally caused intraturmal ONOO<sup>-</sup> boost via cascade reaction. The boosted ONOO<sup>-</sup> could effectively inhibit melanoma by ways of triggering mitochondrion-mediated apoptotic pathway, upregulating 3-nitrotyrosine expression, inducing DNA damage and inhibiting DNA repair enzyme expression of poly (ADP-ribose) polymerase 1 (PARP-1). Moreover, ONOO<sup>-</sup> displayed excellent immunoactivation and immunomodulation activities by effectively inducing immunogenic tumor cell death, promoting dendritic cells maturation, increasing cytotoxic T lymphocytes expression and repolarizing M1-phenotype macrophages.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123045"},"PeriodicalIF":12.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913445","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
Bi2WO6@Cu2O-GOx bio-heterojunctionp-n spray for accelerating chronic diabetic wound repairment with bilaterally enhanced sono-catalysis and glycolytic inhibition antisepsis.
IF 12.8 1区 医学
Biomaterials Pub Date : 2024-12-24 DOI: 10.1016/j.biomaterials.2024.123046
Yandong Wang, Fei Chang, Yutang Li, Fenglong Wang, Can Li, Hui Li, Yanyan Jiang
{"title":"Bi<sub>2</sub>WO<sub>6</sub>@Cu<sub>2</sub>O-GO<sub>x</sub> bio-heterojunction<sub>p-n</sub> spray for accelerating chronic diabetic wound repairment with bilaterally enhanced sono-catalysis and glycolytic inhibition antisepsis.","authors":"Yandong Wang, Fei Chang, Yutang Li, Fenglong Wang, Can Li, Hui Li, Yanyan Jiang","doi":"10.1016/j.biomaterials.2024.123046","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.123046","url":null,"abstract":"<p><p>Chronic diabetic wound poses a pressing global healthcare challenge, necessitating an approach to address issues such as pathogenic bacteria elimination, blood sugar regulation, and angiogenesis stimulation. Herein, we engineered a Bi<sub>2</sub>WO<sub>6</sub>@Cu<sub>2</sub>O-GOx bio-heterojunction (BWCG bio-HJ) with exceptional cascade catalytic performance and impressive sonosensitivity to remodel the wound microenvironment and expedite the diabetic wound healing. Specifically, the Z-scheme junctions of Bi<sub>2</sub>WO<sub>6</sub>@Cu<sub>2</sub>O significantly augmented carrier separation dynamics, leading to the highly efficient generation of reactive oxygen species (ROS) upon US irradiations. Furthermore, glucose oxidase (GOx) grafted on the Bi<sub>2</sub>WO<sub>6</sub>@Cu<sub>2</sub>O surface facilitated the conversion of glucose into H<sub>2</sub>O<sub>2</sub> and glucuronic acid, providing a rich supply for Cu<sup>+</sup>-mediated Fenton-like reactions. The robust oxidation effect disrupted the bacteria's phosphotransferase system (PTS), hindering glucose uptake, glycolysis, and energy metabolism, ultimately inducing bacterial death and reshaping the diabetic wound microenvironment. The BWCG bio-HJ was formulated as an antibacterial spray for chronic diabetic wound repair. Extensive in vitro and in vivo experiments confirmed that the BWCG bio-HJ spray could eliminate pathogenic bacteria, consume local blood sugar, and promote angiogenesis, collagen deposition, and epithelialization, thereby accelerating the diabetic wound healing process. This bio-heterojunction spray comprehensively addressed the principal pathological factors associated with diabetic wounds, offering a promising strategy for combatting stubborn infections.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"317 ","pages":"123046"},"PeriodicalIF":12.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890819","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
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