Pub Date : 2024-11-21DOI: 10.1016/j.biomaterials.2024.122966
Hong Lyun Kim, Gurusamy Saravanakumar, Seowon Lee, Subin Jang, Seonwoo Kang, Mihyeon Park, Sivasangu Sobha, So-Hee Park, Soo-Min Kim, Jung-Ah Lee, Eunkyung Shin, You-Jin Kim, Hye-Sook Jeong, Dokeun Kim, Won Jong Kim
{"title":"Corrigendum to \"Poly(β-amino ester) polymer library with monomer variation for mRNA delivery\" [Biomaterials 314 (2025) 122896].","authors":"Hong Lyun Kim, Gurusamy Saravanakumar, Seowon Lee, Subin Jang, Seonwoo Kang, Mihyeon Park, Sivasangu Sobha, So-Hee Park, Soo-Min Kim, Jung-Ah Lee, Eunkyung Shin, You-Jin Kim, Hye-Sook Jeong, Dokeun Kim, Won Jong Kim","doi":"10.1016/j.biomaterials.2024.122966","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.122966","url":null,"abstract":"","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":" ","pages":"122966"},"PeriodicalIF":12.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692184","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}
Abnormal tumor metabolism leads to tumor growth, metastasis, and recurrence, reprogramming tumor metabolism and activating potent anti-tumor immune response have been demonstrated to have good therapeutic effects on tumor elimination. Copper-based nanomaterials involved in cuproptosis show great prospects in these two aspects, but their efficiency is restricted by Cu homeostasis and the toxicity of the chelator. Here, the pH-responsive AuNRs@Cu2O core-shell plasmonic hybrid nanorods (ACNRs) have been successfully fabricated to realize microenvironment-controlled release at the tumor site for the combined therapy of cuproptosis and photothermal treatment. The AuNRs core exhibited excellent NIR-II photothermal property, which boost the intracellular concentration of copper to trigger severe cuproptosis and induce immunogenic cell death of tumor cells. In vivo studies demonstrated the ACNR exhibited efficient tumor therapy for primary, metastatic, and recurrent tumors. ACNRs-induced cuproptosis and PTT were capable of reprogramming energy metabolism, leading to a decreased production of lactic acid. This potential of metabolic reprogramming assisted in reshaping the immunosuppressive tumor microenvironment to facilitate the infiltration of immune cells and boost the immune responses triggered by PTT. The therapeutic mechanism was further verified by metabolomics analysis, which indicated that ACNRs + PTT treatment led to the inhibition of the Pentose Phosphate Pathway and Glycolysis pathways in tumor cells. The suppression of glycolytic reduced ATP synthesis, thereby hindering energy-dependent copper efflux, which in turn promoted cuproptosis. Taken together, this study offers promising insights for cuproptosis-based cancer treatment and sheds new light on nanomedicine-mediated metabolic modulation for future tumor therapy.
肿瘤代谢异常会导致肿瘤生长、转移和复发，重编程肿瘤代谢和激活强效抗肿瘤免疫反应已被证明对消除肿瘤具有良好的治疗效果。铜基纳米材料参与铜跃迁在这两方面显示出巨大的前景，但其效率受到铜平衡和螯合剂毒性的限制。本文成功制备了pH响应的AuNRs@Cu2O核壳质子杂化纳米棒（ACNRs），实现了肿瘤部位的微环境控制释放，用于杯突疗法和光热疗法的联合治疗。AuNRs 内核表现出优异的近红外-II 光热特性，可提高铜在细胞内的浓度，引发严重的杯突症，诱导肿瘤细胞免疫性死亡。体内研究表明，AcNR 能有效治疗原发性、转移性和复发性肿瘤。ACNR 诱导的杯突症和 PTT 能够重新规划能量代谢，从而减少乳酸的产生。这种代谢重编程的潜力有助于重塑免疫抑制性肿瘤微环境，从而促进免疫细胞的浸润，并增强 PTT 引发的免疫反应。代谢组学分析进一步验证了这一治疗机制，结果表明 ACNRs + PTT 治疗可抑制肿瘤细胞中的磷酸戊糖途径和糖酵解途径。糖酵解的抑制减少了 ATP 的合成，从而阻碍了能量依赖性铜外流，进而促进了杯突症。综上所述，这项研究为基于杯突症的癌症治疗提供了前景广阔的见解，并为纳米药物介导的代谢调节在未来肿瘤治疗中的应用提供了新的启示。
{"title":"Responsive plasmonic hybrid nanorods enables metabolism reprogramming via cuproptosis-photothermal combined cancer therapy.","authors":"Qian Xie, Tao Sun, Liang Zhang, Mingfu Gong, Wansu Zhang, Xu Liu, Yue Zhao, Miaomiao Wang, Xiaofeng Yang, Zhipeng Zhang, Gang Liu, Chunyu Zhou, Dong Zhang","doi":"10.1016/j.biomaterials.2024.122971","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.122971","url":null,"abstract":"<p><p>Abnormal tumor metabolism leads to tumor growth, metastasis, and recurrence, reprogramming tumor metabolism and activating potent anti-tumor immune response have been demonstrated to have good therapeutic effects on tumor elimination. Copper-based nanomaterials involved in cuproptosis show great prospects in these two aspects, but their efficiency is restricted by Cu homeostasis and the toxicity of the chelator. Here, the pH-responsive AuNRs@Cu<sub>2</sub>O core-shell plasmonic hybrid nanorods (ACNRs) have been successfully fabricated to realize microenvironment-controlled release at the tumor site for the combined therapy of cuproptosis and photothermal treatment. The AuNRs core exhibited excellent NIR-II photothermal property, which boost the intracellular concentration of copper to trigger severe cuproptosis and induce immunogenic cell death of tumor cells. In vivo studies demonstrated the ACNR exhibited efficient tumor therapy for primary, metastatic, and recurrent tumors. ACNRs-induced cuproptosis and PTT were capable of reprogramming energy metabolism, leading to a decreased production of lactic acid. This potential of metabolic reprogramming assisted in reshaping the immunosuppressive tumor microenvironment to facilitate the infiltration of immune cells and boost the immune responses triggered by PTT. The therapeutic mechanism was further verified by metabolomics analysis, which indicated that ACNRs + PTT treatment led to the inhibition of the Pentose Phosphate Pathway and Glycolysis pathways in tumor cells. The suppression of glycolytic reduced ATP synthesis, thereby hindering energy-dependent copper efflux, which in turn promoted cuproptosis. Taken together, this study offers promising insights for cuproptosis-based cancer treatment and sheds new light on nanomedicine-mediated metabolic modulation for future tumor therapy.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"122971"},"PeriodicalIF":12.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692186","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}
Pub Date : 2024-11-16DOI: 10.1016/j.biomaterials.2024.122970
Haihua Ji, Yiqun Wan, Shengjie Li, Dexi Zhou, Fengying Gu, Jiajiu Sun, Xiaochen Yan, Yu Le, Tingtao Chen, Shaoping Nie, Hao Wan
Effective, user-friendly, lifestyle-compatible, and economic treatment for type 2 diabetes (T2D) is urgently needed due to its high incidence and health threats. Here, we remolded Lactococcus lactis through genetic engineering to persistently secrete glucagon-like peptide-1 (L. lactis-GLP-1) and subsequent bioorthogonal arming with dopamine (DA)-based "gripper" and β-glucan (GN)-based "shield" (L. lactis-GLP-1-DA@GN) for treatment of T2D mice via oral administration. With protection by GN-based "shield", L. lactis-GLP-1-DA@GN achieved an impressive enhancement of survival by 20666 times compared with bare L. lactis-GLP-1 after experiencing gastrointestinal conditions and DA-based "gripper" was shielded from interaction with the upper digestive tract. Once prebiotic GN was metabolized by gut microbiota into short-chain fatty acids (SCFAs), underlying DA-based "gripper" was exposed to assist intestinal colonization of L. lactis-GLP-1, achieving synergistic treatment effects through secreted GLP-1 and SCFAs. With all advances, oral administration of L. lactis-GLP-1-DA@GN realized effective T2D treatment through improving glucose/lipid homeostasis, repairing major organs' damages, and positively modulating gut microbiota. Moreover, multi-omics analysis revealed that L. lactis-GLP-1-DA@GN also mainly intervened in liver's signaling pathways regarding lipid metabolism and oxidative regulation to advance anti-T2D process. Our strategy marks reconstruction of probiotics by combining chemical and biological tools, broadening the avenue of manipulating probiotics for disease treatments.
{"title":"Remolding probiotics for effective treatment of type 2 diabetes via oral administration.","authors":"Haihua Ji, Yiqun Wan, Shengjie Li, Dexi Zhou, Fengying Gu, Jiajiu Sun, Xiaochen Yan, Yu Le, Tingtao Chen, Shaoping Nie, Hao Wan","doi":"10.1016/j.biomaterials.2024.122970","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.122970","url":null,"abstract":"<p><p>Effective, user-friendly, lifestyle-compatible, and economic treatment for type 2 diabetes (T2D) is urgently needed due to its high incidence and health threats. Here, we remolded Lactococcus lactis through genetic engineering to persistently secrete glucagon-like peptide-1 (L. lactis-GLP-1) and subsequent bioorthogonal arming with dopamine (DA)-based \"gripper\" and β-glucan (GN)-based \"shield\" (L. lactis-GLP-1-DA@GN) for treatment of T2D mice via oral administration. With protection by GN-based \"shield\", L. lactis-GLP-1-DA@GN achieved an impressive enhancement of survival by 20666 times compared with bare L. lactis-GLP-1 after experiencing gastrointestinal conditions and DA-based \"gripper\" was shielded from interaction with the upper digestive tract. Once prebiotic GN was metabolized by gut microbiota into short-chain fatty acids (SCFAs), underlying DA-based \"gripper\" was exposed to assist intestinal colonization of L. lactis-GLP-1, achieving synergistic treatment effects through secreted GLP-1 and SCFAs. With all advances, oral administration of L. lactis-GLP-1-DA@GN realized effective T2D treatment through improving glucose/lipid homeostasis, repairing major organs' damages, and positively modulating gut microbiota. Moreover, multi-omics analysis revealed that L. lactis-GLP-1-DA@GN also mainly intervened in liver's signaling pathways regarding lipid metabolism and oxidative regulation to advance anti-T2D process. Our strategy marks reconstruction of probiotics by combining chemical and biological tools, broadening the avenue of manipulating probiotics for disease treatments.</p>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"122970"},"PeriodicalIF":12.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692185","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}
Pub Date : 2024-11-15DOI: 10.1016/j.biomaterials.2024.122969
Xiaoyu Wang , Weijie Chi , Jiao Wu , Jingwen Zou , Jiyoung Yoo , Seokjin Hong , Fan Zhang , Zhiqiang Mao , Jong Seung Kim
Pyroptosis is considered as a new way to effectively boost the immune response of tumors and inhibit tumor growth. Effective strategies to induce pyroptosis mainly rely on chemotherapeutic drugs and phototherapy, but their potential biotoxicity and phototoxicity limit their application in biomedicine. Herein, we designed a NIR-II emitting pyroptosis biotuner, Rd-TTPA, which induced pyroptosis under ultrasound irradiation to achieve pyroptosis-enhanced sonodynamic therapy (SDT) and immunogenic cell death (ICD) for tumors. Benefiting from its A-π-D1-D2 structure enhanced donor-acceptor interaction, Rd-TTPA can induce cell pyroptosis under both normoxia (21 % O2) and hypoxia (2 % O2) conditions by rapidly generating superoxide radicals (O2−•) upon ultrasound irradiation. The sonodynamic biotuner of pyroptosis overcomes the longstanding weakness of chemical drug and photosensitizer-based pyroptosis, such as drug resistance and limited penetration depth. In-depth studies demonstrated that Rd-TTPA can selectively target tumor cell mitochondria and possess excellent in vivo NIR-II fluorescence imaging capabilities. Administrating a tumor-bearing mouse model with Rd-TPPA, satisfying antitumor efficacy via pyroptosis-augmented SDT was achieved upon the guidance of NIR-II fluorescence imaging.
热休克被认为是有效提高肿瘤免疫反应和抑制肿瘤生长的一种新方法。诱导热休克的有效策略主要依靠化疗药物和光疗，但其潜在的生物毒性和光毒性限制了它们在生物医学中的应用。在此，我们设计了一种发射近红外Ⅱ射线的热休克生物调控剂--Rd-TTPA，它能在超声照射下诱导热休克，从而实现热休克增强声动力疗法（SDT）和肿瘤免疫性细胞死亡（ICD）。Rd-TTPA的A-π-D1-D2结构增强了供体与受体之间的相互作用，在正常缺氧（21% O2）和缺氧（2% O2）条件下，Rd-TTPA都能在超声波照射下通过快速产生超氧自由基（O2--）诱导细胞热解。热释电的声动力生物调谐器克服了长期以来基于化学药物和光敏剂的热释电的弱点，如耐药性和有限的渗透深度。深入研究表明，Rd-TTPA 可选择性地靶向肿瘤细胞线粒体，并具有出色的体内近红外 II 荧光成像能力。在肿瘤小鼠模型中使用Rd-TTPA，在近红外-II荧光成像的指导下，通过热渗透增强的SDT获得了满意的抗肿瘤疗效。
{"title":"A NIR-II emissive sonosensitized biotuner for pyroptosis-enhanced sonodynamic therapy of hypoxic tumors","authors":"Xiaoyu Wang , Weijie Chi , Jiao Wu , Jingwen Zou , Jiyoung Yoo , Seokjin Hong , Fan Zhang , Zhiqiang Mao , Jong Seung Kim","doi":"10.1016/j.biomaterials.2024.122969","DOIUrl":"10.1016/j.biomaterials.2024.122969","url":null,"abstract":"<div><div>Pyroptosis is considered as a new way to effectively boost the immune response of tumors and inhibit tumor growth. Effective strategies to induce pyroptosis mainly rely on chemotherapeutic drugs and phototherapy, but their potential biotoxicity and phototoxicity limit their application in biomedicine. Herein, we designed a NIR-II emitting pyroptosis biotuner, <strong>Rd-TTPA</strong>, which induced pyroptosis under ultrasound irradiation to achieve pyroptosis-enhanced sonodynamic therapy (SDT) and immunogenic cell death (ICD) for tumors. Benefiting from its A-π-D<sub>1</sub>-D<sub>2</sub> structure enhanced donor-acceptor interaction, <strong>Rd-TTPA</strong> can induce cell pyroptosis under both normoxia (21 % O<sub>2</sub>) and hypoxia (2 % O<sub>2</sub>) conditions by rapidly generating superoxide radicals (O<sub>2</sub><sup>−•</sup>) upon ultrasound irradiation. The sonodynamic biotuner of pyroptosis overcomes the longstanding weakness of chemical drug and photosensitizer-based pyroptosis, such as drug resistance and limited penetration depth. In-depth studies demonstrated that <strong>Rd-TTPA</strong> can selectively target tumor cell mitochondria and possess excellent <em>in vivo</em> NIR-II fluorescence imaging capabilities. Administrating a tumor-bearing mouse model with <strong>Rd-TPPA</strong>, satisfying antitumor efficacy <em>via</em> pyroptosis-augmented SDT was achieved upon the guidance of NIR-II fluorescence imaging.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122969"},"PeriodicalIF":12.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646041","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}
Pub Date : 2024-11-15DOI: 10.1016/j.biomaterials.2024.122968
Ling Mei , Qihang Ding , Yuxin Xie , Haowei Liu , Hongping Li , Eunji Kim , Xue Shen , Yibin Zhang , Shuai Zhang , Jong Seung Kim
Delivering nanoparticles to deep tumor tissues while maintaining high therapeutic efficacy and minimizing damage to surrounding tissues has long posed a significant challenge. To address this, we have developed innovative self-propelling bowl-shaped nanomotors MSLA@GOx-PDA composed of mesoporous silica loaded with l-arginine and polydopamine, along with glucose oxidase (GOx). These nanomotors facilitate the generation of hydrogen peroxide through GOx-catalyzed glucose oxidation, thereby initiating nitric oxide production from l-arginine. This dual mechanism equips MSLA@GOx-PDA with the robust motility required for deep tumor tissue penetration while depleting essential nutrients necessary for tumor growth, consequently impeding tumor progression. In addition, near-infrared lasers have the significant advantage of being depth-penetrating and non-invasive, allowing real-time fluorescence imaging and guiding dopamine-mediated mild photothermal therapy. Notably, starvation therapy depletes intracellular adenosine triphosphate and inhibits the synthesis of heat shock proteins, thus overcoming the Achilles' heel of mild photothermal therapy and significantly enhancing the efficacy of this therapy with encouraging synergistic anti-tumour effects. Overall, the integration of biochemical and optics strategies in this nanomotor platform represents a significant advancement in deep-tissue tumor therapy. It has substantial clinical translational value and is expected to have a transformative impact on future cancer treatments.
{"title":"Self-propelling intelligent nanomotor: A dual-action photothermal and starvation strategy for targeted deep tumor destruction","authors":"Ling Mei , Qihang Ding , Yuxin Xie , Haowei Liu , Hongping Li , Eunji Kim , Xue Shen , Yibin Zhang , Shuai Zhang , Jong Seung Kim","doi":"10.1016/j.biomaterials.2024.122968","DOIUrl":"10.1016/j.biomaterials.2024.122968","url":null,"abstract":"<div><div>Delivering nanoparticles to deep tumor tissues while maintaining high therapeutic efficacy and minimizing damage to surrounding tissues has long posed a significant challenge. To address this, we have developed innovative self-propelling bowl-shaped nanomotors MSLA@GOx-PDA composed of mesoporous silica loaded with <span><em>l</em></span>-arginine and polydopamine, along with glucose oxidase (GOx). These nanomotors facilitate the generation of hydrogen peroxide through GOx-catalyzed glucose oxidation, thereby initiating nitric oxide production from <span><em>l</em></span>-arginine. This dual mechanism equips MSLA@GOx-PDA with the robust motility required for deep tumor tissue penetration while depleting essential nutrients necessary for tumor growth, consequently impeding tumor progression. In addition, near-infrared lasers have the significant advantage of being depth-penetrating and non-invasive, allowing real-time fluorescence imaging and guiding dopamine-mediated mild photothermal therapy. Notably, starvation therapy depletes intracellular adenosine triphosphate and inhibits the synthesis of heat shock proteins, thus overcoming the Achilles' heel of mild photothermal therapy and significantly enhancing the efficacy of this therapy with encouraging synergistic anti-tumour effects. Overall, the integration of biochemical and optics strategies in this nanomotor platform represents a significant advancement in deep-tissue tumor therapy. It has substantial clinical translational value and is expected to have a transformative impact on future cancer treatments.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122968"},"PeriodicalIF":12.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660867","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}
Pub Date : 2024-11-12DOI: 10.1016/j.biomaterials.2024.122962
Zongyan He , Qian Wang , Jun Du , Sijia Wu , Qing Miao , Yuhao Li , Yuqing Miao , Jingxiang Wu
Inducing reactive oxygen species (ROS) via sonocatalysis to initiate inflammatory programmed cell death (PANoptosis) and immunogenic cell death (ICD) presents a promising strategy for activatable cancer immunotherapy. However, the limited ROS generation by sonosensitizers under ultrasound and the immunosuppressive tumor microenvironment hinder the efficiency of sono-immunotherapy. To overcome these challenges, a bismuth-based ternary heterojunction, Bi@Bi2O3–Pt-PEG (BBOP), was developed for sonocatalytic therapy aimed at activating immune responses. This system enhances ROS production during sonocatalysis and leverages dual therapeutic mechanisms by inducing PANoptosis and ICD to achieve improved anti-tumor efficacy. BBOP forms a Z-scheme heterojunction and Schottky contact through the formation of an intermediate Bi2O3 layer and the introduction of Pt. These structures significantly enhance sonocatalytic activity, while the Pt nanozyme exhibits catalase-like behavior, supplying oxygen for sonocatalysis, boosting ROS generation, and effectively relieving tumor hypoxia to reduce immune suppression. Further in vitro and in vivo experiments confirmed BBOP's ability to activate immune responses under ultrasound, inhibiting tumor growth and metastasis. RNA sequencing revealed the therapeutic biological mechanisms. The construction of this catalytic system not only provides insights for optimizing sonosensitizers but also offers a safer and more effective sono-immunotherapy activation strategy and theoretical basis for clinical cancer treatment.
{"title":"Overcoming tumor hypoxic bismuth-based ternary heterojunctions enable defect modulation-augmented tumor sonocatalytic immunotherapy","authors":"Zongyan He , Qian Wang , Jun Du , Sijia Wu , Qing Miao , Yuhao Li , Yuqing Miao , Jingxiang Wu","doi":"10.1016/j.biomaterials.2024.122962","DOIUrl":"10.1016/j.biomaterials.2024.122962","url":null,"abstract":"<div><div>Inducing reactive oxygen species (ROS) via sonocatalysis to initiate inflammatory programmed cell death (PANoptosis) and immunogenic cell death (ICD) presents a promising strategy for activatable cancer immunotherapy. However, the limited ROS generation by sonosensitizers under ultrasound and the immunosuppressive tumor microenvironment hinder the efficiency of sono-immunotherapy. To overcome these challenges, a bismuth-based ternary heterojunction, Bi@Bi<sub>2</sub>O<sub>3</sub>–Pt-PEG (BBOP), was developed for sonocatalytic therapy aimed at activating immune responses. This system enhances ROS production during sonocatalysis and leverages dual therapeutic mechanisms by inducing PANoptosis and ICD to achieve improved anti-tumor efficacy. BBOP forms a Z-scheme heterojunction and Schottky contact through the formation of an intermediate Bi<sub>2</sub>O<sub>3</sub> layer and the introduction of Pt. These structures significantly enhance sonocatalytic activity, while the Pt nanozyme exhibits catalase-like behavior, supplying oxygen for sonocatalysis, boosting ROS generation, and effectively relieving tumor hypoxia to reduce immune suppression. Further <em>in vitro</em> and <em>in vivo</em> experiments confirmed BBOP's ability to activate immune responses under ultrasound, inhibiting tumor growth and metastasis. RNA sequencing revealed the therapeutic biological mechanisms. The construction of this catalytic system not only provides insights for optimizing sonosensitizers but also offers a safer and more effective sono-immunotherapy activation strategy and theoretical basis for clinical cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122962"},"PeriodicalIF":12.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660866","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}
Pub Date : 2024-11-12DOI: 10.1016/j.biomaterials.2024.122960
Pingting Ye , Chunhui Wang , Yixuan Wen, Kang Fang, Qi Li, Xin Zhang, Jingxian Yang, Ruihao Li, Mengyao Chen, Xiaohan Tong, Shuo Shi, Chunyan Dong
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer due to poor immunogenicity and limited immune cell infiltration, efficient therapeutics are still deficiency. Ferroptosis, a reactive oxygen species (ROS)-reliant cell death, can enhance cellular immunogenicity and then active immune system. To sustain a long-term “hot” tumour immune microenvironment (TIME), an immune-modulator is indispensable. Metformin (MET), a commonly used oral drug for type 2 diabetes, has played a vital role in fostering an immunostimulatory environment. Herein, we confirm the TIME can be remodeled by MET and further promotes ferroptosis via upregulating cellular concentration of l-Glutamine. In light of this, we have design a self-assembled MET-loaded Fe3+-doped polydopamine nanoparticle (Fe-PDA-MET NP) that can disorder the cellular redox homeostasis and induce robust ferroptosis under 808 nm irradiation, resulting in a strong immune response. Based on the function of MET, there is a marked increase in the infiltration of activated CD8+ T cells and NK cells, which subsequently augments ferroptosis to a greater extent. Taken together, Fe-PDA-MET NPs activate a ferroptotic positive-feedback loop for effectively control TNBC progression, which offers a promising therapeutic modality to enhance the immunogenicity and reshape the TIME.
三阴性乳腺癌（TNBC）是一种侵袭性特别强的乳腺癌亚型，由于其免疫原性差、免疫细胞浸润有限，目前仍缺乏有效的治疗方法。铁突变是一种依赖活性氧（ROS）的细胞死亡，它能增强细胞免疫原性，进而活跃免疫系统。要维持长期的 "热 "肿瘤免疫微环境（TIME），免疫调节剂必不可少。二甲双胍（MET）是治疗2型糖尿病的常用口服药物，在促进免疫刺激环境方面发挥了重要作用。在此，我们证实二甲双胍可重塑TIME，并通过上调细胞中l-谷氨酰胺的浓度进一步促进铁突变。有鉴于此，我们设计了一种自组装的MET负载型Fe3+掺杂多巴胺纳米粒子（Fe-PDA-MET NP），它能在808 nm照射下扰乱细胞氧化还原平衡并诱导强有力的铁突变，从而产生强烈的免疫反应。基于 MET 的功能，活化的 CD8+ T 细胞和 NK 细胞的浸润明显增加，从而在更大程度上增强了铁凋亡。综上所述，Fe-PDA-MET NPs能激活铁凋亡正反馈循环，有效控制TNBC的进展，为增强免疫原性和重塑TIME提供了一种前景广阔的治疗模式。
{"title":"A positive-feedback loop suppresses TNBC tumour growth by remodeling tumour immune microenvironment and inducing ferroptosis","authors":"Pingting Ye , Chunhui Wang , Yixuan Wen, Kang Fang, Qi Li, Xin Zhang, Jingxian Yang, Ruihao Li, Mengyao Chen, Xiaohan Tong, Shuo Shi, Chunyan Dong","doi":"10.1016/j.biomaterials.2024.122960","DOIUrl":"10.1016/j.biomaterials.2024.122960","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer due to poor immunogenicity and limited immune cell infiltration, efficient therapeutics are still deficiency. Ferroptosis, a reactive oxygen species (ROS)-reliant cell death, can enhance cellular immunogenicity and then active immune system. To sustain a long-term “hot” tumour immune microenvironment (TIME), an immune-modulator is indispensable. Metformin (MET), a commonly used oral drug for type 2 diabetes, has played a vital role in fostering an immunostimulatory environment. Herein, we confirm the TIME can be remodeled by MET and further promotes ferroptosis via upregulating cellular concentration of <span>l</span>-Glutamine. In light of this, we have design a self-assembled MET-loaded Fe<sup>3+</sup>-doped polydopamine nanoparticle (Fe-PDA-MET NP) that can disorder the cellular redox homeostasis and induce robust ferroptosis under 808 nm irradiation, resulting in a strong immune response. Based on the function of MET, there is a marked increase in the infiltration of activated CD8<sup>+</sup> T cells and NK cells, which subsequently augments ferroptosis to a greater extent. Taken together, Fe-PDA-MET NPs activate a ferroptotic positive-feedback loop for effectively control TNBC progression, which offers a promising therapeutic modality to enhance the immunogenicity and reshape the TIME.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122960"},"PeriodicalIF":12.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613383","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}
Pub Date : 2024-11-12DOI: 10.1016/j.biomaterials.2024.122963
Steven M. Wellman , Adam M. Forrest , Madeline M. Douglas , Ashwat Subbaraman , Guangfeng Zhang , Takashi D.Y. Kozai
Integration of neural interfaces with minimal tissue disruption in the brain is ideal to develop robust tools that can address essential neuroscience questions and combat neurological disorders. However, implantation of intracortical devices provokes severe tissue inflammation within the brain, which requires a high metabolic demand to support a complex series of cellular events mediating tissue degeneration and wound healing. Pericytes, peri-vascular cells involved in blood-brain barrier maintenance, vascular permeability, waste clearance, and angiogenesis, have recently been implicated as potential perpetuators of neurodegeneration in brain injury and disease. While the intimate relationship between pericytes and the cortical microvasculature have been explored in other disease states, their behavior following microelectrode implantation, which is responsible for direct blood vessel disruption and dysfunction, is currently unknown. Using two-photon microscopy we observed dynamic changes in the structure and function of pericytes during implantation of a microelectrode array over a 4-week implantation period. Pericytes respond to electrode insertion through transient increases in intracellular calcium and underlying constriction of capillary vessels. Within days following the initial insertion, we observed an influx of new, proliferating pericytes which contribute to new blood vessel formation. Additionally, we discovered a potentially novel population of reactive immune cells in close proximity to the electrode-tissue interface actively engaging in encapsulation of the microelectrode array. Finally, we determined that intracellular pericyte calcium can be modulated by intracortical microstimulation in an amplitude- and frequency-dependent manner. This study provides a new perspective on the complex biological sequelae occurring at the electrode-tissue interface and will foster new avenues of potential research consideration and lead to development of more advanced therapeutic interventions towards improving the biocompatibility of neural electrode technology.
{"title":"Dynamic changes in the structure and function of brain mural cells around chronically implanted microelectrodes","authors":"Steven M. Wellman , Adam M. Forrest , Madeline M. Douglas , Ashwat Subbaraman , Guangfeng Zhang , Takashi D.Y. Kozai","doi":"10.1016/j.biomaterials.2024.122963","DOIUrl":"10.1016/j.biomaterials.2024.122963","url":null,"abstract":"<div><div>Integration of neural interfaces with minimal tissue disruption in the brain is ideal to develop robust tools that can address essential neuroscience questions and combat neurological disorders. However, implantation of intracortical devices provokes severe tissue inflammation within the brain, which requires a high metabolic demand to support a complex series of cellular events mediating tissue degeneration and wound healing. Pericytes, peri-vascular cells involved in blood-brain barrier maintenance, vascular permeability, waste clearance, and angiogenesis, have recently been implicated as potential perpetuators of neurodegeneration in brain injury and disease. While the intimate relationship between pericytes and the cortical microvasculature have been explored in other disease states, their behavior following microelectrode implantation, which is responsible for direct blood vessel disruption and dysfunction, is currently unknown. Using two-photon microscopy we observed dynamic changes in the structure and function of pericytes during implantation of a microelectrode array over a 4-week implantation period. Pericytes respond to electrode insertion through transient increases in intracellular calcium and underlying constriction of capillary vessels. Within days following the initial insertion, we observed an influx of new, proliferating pericytes which contribute to new blood vessel formation. Additionally, we discovered a potentially novel population of reactive immune cells in close proximity to the electrode-tissue interface actively engaging in encapsulation of the microelectrode array. Finally, we determined that intracellular pericyte calcium can be modulated by intracortical microstimulation in an amplitude- and frequency-dependent manner. This study provides a new perspective on the complex biological sequelae occurring at the electrode-tissue interface and will foster new avenues of potential research consideration and lead to development of more advanced therapeutic interventions towards improving the biocompatibility of neural electrode technology.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122963"},"PeriodicalIF":12.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-healing diabetic foot ulcers are the knotty public health issue due to the uncontrolled bacterial infection, prolonged inflammation, and inferior vessel remodeling. In this work, polypyrrole (Ppy) was added into the hybrid hydrogel containing polyvinyl alcohol (PVA), polyethylene glycol (PEG), and hyaluronan (HA) to acquire superior mechanism and photothermal ability. The Ppy composited hybrid hydrogel could effectively kill bacteria through accumulating heat on the hydrogel surface. RNA-Seq analysis shows that the heat accumulation could enhance phagosome of macrophage and M1 activation, which further accelerate bacteria clearance. Benefitting from the bacteria clearance, macrophage could transform its phenotype to M2 in Ppy composited hybrid hydrogel group with near infrared light (NIR) stimulation. The related genes expression in keratinization, keratinocyte differentiation, and establishment of the skin barrier in the skin were up-regulated and collagen and vascular endothelial growth factor (VEGF) expression level are also enhanced. In summary, Ppy composited hybrid hydrogel could effectively solve the issues of infection and poor wound healing in diabetic foot ulcers, making it an ideal candidate dressing for the treatment of chronic wounds.
{"title":"Self-healing Ppy-hydrogel promotes diabetic skin wound healing through enhanced sterilization and macrophage orchestration triggered by NIR","authors":"Zhuangzhuang Chu , Xingdan Liu , Tong Zhao , Dongya Jiang , Jing Zhao , Xiaohua Dong , Kelvin W.K. Yeung , Xuanyong Liu , Yun Liao , Liping Ouyang","doi":"10.1016/j.biomaterials.2024.122964","DOIUrl":"10.1016/j.biomaterials.2024.122964","url":null,"abstract":"<div><div>Non-healing diabetic foot ulcers are the knotty public health issue due to the uncontrolled bacterial infection, prolonged inflammation, and inferior vessel remodeling. In this work, polypyrrole (Ppy) was added into the hybrid hydrogel containing polyvinyl alcohol (PVA), polyethylene glycol (PEG), and hyaluronan (HA) to acquire superior mechanism and photothermal ability. The Ppy composited hybrid hydrogel could effectively kill bacteria through accumulating heat on the hydrogel surface. RNA-Seq analysis shows that the heat accumulation could enhance phagosome of macrophage and M1 activation, which further accelerate bacteria clearance. Benefitting from the bacteria clearance, macrophage could transform its phenotype to M2 in Ppy composited hybrid hydrogel group with near infrared light (NIR) stimulation. The related genes expression in keratinization, keratinocyte differentiation, and establishment of the skin barrier in the skin were up-regulated and collagen and vascular endothelial growth factor (VEGF) expression level are also enhanced. In summary, Ppy composited hybrid hydrogel could effectively solve the issues of infection and poor wound healing in diabetic foot ulcers, making it an ideal candidate dressing for the treatment of chronic wounds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122964"},"PeriodicalIF":12.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646082","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号