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Self-luminous nanoengineered bacteria with the sustained release of interleukin 2 as an in situ vaccine for enhanced cancer immunotherapy 具有白细胞介素 2 持续释放功能的自发光纳米工程细菌作为原位疫苗用于增强癌症免疫疗法。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-26 DOI: 10.1016/j.actbio.2025.03.046
Guannan Liu , Huiqin Wang , Zhengyue Fei , Xinyue Tao , Jiamin Zheng , Guohao Cai , Xueming Li , Junlong Zhuang , Hao Ren
Bacteria-based in situ vaccination (ISV) has emerged as an effective therapeutic approach by activating anti-tumor immunity. However, inducing immunogenic cell death (ICD) and promoting effector T cell activation remain critical challenges in clinical applications of bacteria-based ISV. Here, we have developed a tumor microenvironment-activated nano-hybrid engineered bacterium as ISV. It was engineered with a blue-light response module (EL222) and self-luminous luminal hyaluronic acid (LHA) nanoparticles. Our study demonstrates that LHA generates local blue light stimulated by hydrogen peroxide, non-invasively activating the engineered Escherichia coli to produce IL-2. The engineered bacteria serve as an immunological adjuvant, promoting dendritic cell maturation, synergistically promoting T cell infiltration, and ultimately triggering a comprehensive activation of the immune system. Furthermore, when combined with the immune checkpoint inhibitor anti-PD-L1, this approach further effectively enhances cancer immunotherapy. Our results provide new strategies and promising prospects for the development of bacteria-based ISV immunotherapy.

Statement of significance

This study developed a tumor microenvironment-activated nano-hybrid engineered bacteria (Ec-mIL2@LHA) as in situ vaccine for enhanced cancer immunotherapy. The LHA in bacterial vaccine non-invasively generated blue light upon stimulation by hydrogen peroxide of TME, leading to the sustained release of low-dose IL2 by engineered bacteria. In vitro and in vivo studies have demonstrated the bacterial in situ vaccine induced the immunogenic cell death and promote maturation of dendritic cells, ultimately triggering a comprehensive activation of anti-tumor immunity. After combination with anti-PD-L1, the bacterial in situ vaccine further effectively enhance cancer immunotherapy and inhibit metastasis. We provide a promising strategy to amplify antitumor immune effects by an engineered bacterial vaccine, showing potential clinical applications.
{"title":"Self-luminous nanoengineered bacteria with the sustained release of interleukin 2 as an in situ vaccine for enhanced cancer immunotherapy","authors":"Guannan Liu ,&nbsp;Huiqin Wang ,&nbsp;Zhengyue Fei ,&nbsp;Xinyue Tao ,&nbsp;Jiamin Zheng ,&nbsp;Guohao Cai ,&nbsp;Xueming Li ,&nbsp;Junlong Zhuang ,&nbsp;Hao Ren","doi":"10.1016/j.actbio.2025.03.046","DOIUrl":"10.1016/j.actbio.2025.03.046","url":null,"abstract":"<div><div>Bacteria-based <em>in situ</em> vaccination (ISV) has emerged as an effective therapeutic approach by activating anti-tumor immunity. However, inducing immunogenic cell death (ICD) and promoting effector T cell activation remain critical challenges in clinical applications of bacteria-based ISV. Here, we have developed a tumor microenvironment-activated nano-hybrid engineered bacterium as ISV. It was engineered with a blue-light response module (EL222) and self-luminous luminal hyaluronic acid (LHA) nanoparticles. Our study demonstrates that LHA generates local blue light stimulated by hydrogen peroxide, non-invasively activating the engineered <em>Escherichia coli</em> to produce IL-2. The engineered bacteria serve as an immunological adjuvant, promoting dendritic cell maturation, synergistically promoting T cell infiltration, and ultimately triggering a comprehensive activation of the immune system. Furthermore, when combined with the immune checkpoint inhibitor anti-PD-L1, this approach further effectively enhances cancer immunotherapy. Our results provide new strategies and promising prospects for the development of bacteria-based ISV immunotherapy.</div></div><div><h3>Statement of significance</h3><div>This study developed a tumor microenvironment-activated nano-hybrid engineered bacteria (Ec-mIL2@LHA) as <em>in situ</em> vaccine for enhanced cancer immunotherapy. The LHA in bacterial vaccine non-invasively generated blue light upon stimulation by hydrogen peroxide of TME, leading to the sustained release of low-dose IL2 by engineered bacteria. <em>In vitro</em> and <em>in vivo</em> studies have demonstrated the bacterial <em>in situ</em> vaccine induced the immunogenic cell death and promote maturation of dendritic cells, ultimately triggering a comprehensive activation of anti-tumor immunity. After combination with anti-PD-L1, the bacterial <em>in situ</em> vaccine further effectively enhance cancer immunotherapy and inhibit metastasis. We provide a promising strategy to amplify antitumor immune effects by an engineered bacterial vaccine, showing potential clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 386-399"},"PeriodicalIF":9.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744606","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
Advances in nanodelivery systems based on apoptosis strategies for enhanced rheumatoid arthritis therapy
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-26 DOI: 10.1016/j.actbio.2025.03.043
Zongquan Zhang , Yilin Liu , Xiaoya Liang , Qian Wang , Maochang Xu , Xi Yang , Jun Tang , Xinghui He , Yufeng He , Dan Zhang , Chunhong Li
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder primarily characterized by persistent synovial inflammation and progressive bone erosion. The pathogenesis of RA involves a complex cascade of cellular and molecular events, including sustained hyperactivation of macrophages, excessive recruitment and activation of neutrophils, pathological proliferation and invasion of fibroblast-like synoviocytes (FLS), and dysregulated differentiation and function of osteoclasts (OCs). The inflammatory factors secreted by these dysregulated cells significantly disrupt the joint microenvironment through multiple pathological mechanisms, primarily by promoting synovial inflammation, cartilage matrix degradation, osteoclast-mediated bone erosion, and pathological angiogenesis. Therapeutic strategies targeting the induction of apoptosis in these malignant cells have demonstrated considerable potential in preclinical studies, offering a promising approach to enhance treatment outcomes by simultaneously reducing inflammatory cytokine production and inhibiting pathogenic cell proliferation. However, conventional therapeutic drugs are limited in clinical applications because of their high toxicity and side effects. Inflammation induces morphological and functional changes in cells within the rheumatoid arthritis microenvironment (RAM), particularly the overexpression of specific receptors on cell membranes. This phenomenon has driven the development of ligand-modified targeted nanodelivery systems (NDSs), which can specifically target and induce apoptosis in specific cell types, thereby enhancing therapeutic efficacy. This paper comprehensively reviews the research progress of targeted NDSs based on apoptosis strategies for RA therapy, with a detailed discussion of their advantages in inducing apoptosis in various disease-associated cells. Furthermore, the potential of combining apoptosis of multiple cell types for RA treatment is explored. This review is expected to improve insights into the apoptosis of malignant cells to enhance RA therapy.

Statement of Significance

This review highlights recent advances in nanodelivery systems (NDSs) based on apoptotic strategies for enhanced rheumatoid arthritis (RA) therapy. Unlike conventional NDSs, these optimized systems specifically induce apoptosis in malignant cells within the RA microenvironment by integrating multiple therapeutic strategies. By summarizing the latest research, our work demonstrates the potential of these NDSs to suppress inflammatory responses and prevent bone destruction through targeted elimination of malignant cells, offering a novel direction for RA treatment. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective therapeutic approaches for RA and other chronic inflammatory diseases.
{"title":"Advances in nanodelivery systems based on apoptosis strategies for enhanced rheumatoid arthritis therapy","authors":"Zongquan Zhang ,&nbsp;Yilin Liu ,&nbsp;Xiaoya Liang ,&nbsp;Qian Wang ,&nbsp;Maochang Xu ,&nbsp;Xi Yang ,&nbsp;Jun Tang ,&nbsp;Xinghui He ,&nbsp;Yufeng He ,&nbsp;Dan Zhang ,&nbsp;Chunhong Li","doi":"10.1016/j.actbio.2025.03.043","DOIUrl":"10.1016/j.actbio.2025.03.043","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder primarily characterized by persistent synovial inflammation and progressive bone erosion. The pathogenesis of RA involves a complex cascade of cellular and molecular events, including sustained hyperactivation of macrophages, excessive recruitment and activation of neutrophils, pathological proliferation and invasion of fibroblast-like synoviocytes (FLS), and dysregulated differentiation and function of osteoclasts (OCs). The inflammatory factors secreted by these dysregulated cells significantly disrupt the joint microenvironment through multiple pathological mechanisms, primarily by promoting synovial inflammation, cartilage matrix degradation, osteoclast-mediated bone erosion, and pathological angiogenesis. Therapeutic strategies targeting the induction of apoptosis in these malignant cells have demonstrated considerable potential in preclinical studies, offering a promising approach to enhance treatment outcomes by simultaneously reducing inflammatory cytokine production and inhibiting pathogenic cell proliferation. However, conventional therapeutic drugs are limited in clinical applications because of their high toxicity and side effects. Inflammation induces morphological and functional changes in cells within the rheumatoid arthritis microenvironment (RAM), particularly the overexpression of specific receptors on cell membranes. This phenomenon has driven the development of ligand-modified targeted nanodelivery systems (NDSs), which can specifically target and induce apoptosis in specific cell types, thereby enhancing therapeutic efficacy. This paper comprehensively reviews the research progress of targeted NDSs based on apoptosis strategies for RA therapy, with a detailed discussion of their advantages in inducing apoptosis in various disease-associated cells. Furthermore, the potential of combining apoptosis of multiple cell types for RA treatment is explored. This review is expected to improve insights into the apoptosis of malignant cells to enhance RA therapy.</div></div><div><h3>Statement of Significance</h3><div>This review highlights recent advances in nanodelivery systems (NDSs) based on apoptotic strategies for enhanced rheumatoid arthritis (RA) therapy. Unlike conventional NDSs, these optimized systems specifically induce apoptosis in malignant cells within the RA microenvironment by integrating multiple therapeutic strategies. By summarizing the latest research, our work demonstrates the potential of these NDSs to suppress inflammatory responses and prevent bone destruction through targeted elimination of malignant cells, offering a novel direction for RA treatment. This review is significant as it provides a comprehensive overview for researchers and clinicians, facilitating the development of more effective therapeutic approaches for RA and other chronic inflammatory diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 87-103"},"PeriodicalIF":9.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744597","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
Recent advances in blood-brain barrier-on-a-chip models
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-22 DOI: 10.1016/j.actbio.2025.03.041
Johanna Vetter , Ilaria Palagi , Ari Waisman , Andreas Blaeser
The blood-brain barrier is a physiological barrier between the vascular system and the nervous system. Under healthy conditions, it restricts the passage of most biomolecules into the brain, making drug development exceedingly challenging. Conventional cell-based in vitro models provide valuable insights into certain features of the BBB. Nevertheless, these models often lack the three-dimensional structure and dynamic interactions of the surrounding microenvironment, which greatly influence cell functionality. Consequently, considerable efforts have been made to enhance in vitro models for drug development and disease research. Recently, microfluidic organ-on-a-chip systems have emerged as promising candidates to better mimic the dynamic nature of the BBB. This review provides a comprehensive overview of recent BBB-on-chip devices. The typical building blocks, chip designs, the perfusion infrastructure, and readouts used to characterize and evaluate BBB formation are presented, analyzed, and discussed in detail.

Statement of Significance

The blood-brain barrier (BBB) is a highly selective barrier that controls what can enter the brain. While it protects the brain from harmful substances, it also hinders the delivery of treatments for neurological diseases such as Alzheimer's and Parkinson's. Due to its complexity, studying the BBB in living organisms remains difficult. However, recent advances in “organ-on-a-chip” technology have allowed scientists to create small, engineered models that replicate the BBB. These models provide a powerful platform to study diseases and test potential drugs with greater accuracy than traditional methods. Organ-on-a-chip devices are designed to mimic the behavior of organs or tissues in the human body, offering a more realistic and controlled environment for research. This review highlights recent breakthroughs in BBB-on-a-chip technology, showing how these models enhance current research and have the potential to transform the way we study brain diseases and develop new drugs. By integrating biology and engineering, BBB-on-a-chip technology has the potential to transform neuroscience research, improve drug development, and enhance our understanding of brain disorders.
{"title":"Recent advances in blood-brain barrier-on-a-chip models","authors":"Johanna Vetter ,&nbsp;Ilaria Palagi ,&nbsp;Ari Waisman ,&nbsp;Andreas Blaeser","doi":"10.1016/j.actbio.2025.03.041","DOIUrl":"10.1016/j.actbio.2025.03.041","url":null,"abstract":"<div><div>The blood-brain barrier is a physiological barrier between the vascular system and the nervous system. Under healthy conditions, it restricts the passage of most biomolecules into the brain, making drug development exceedingly challenging. Conventional cell-based in vitro models provide valuable insights into certain features of the BBB. Nevertheless, these models often lack the three-dimensional structure and dynamic interactions of the surrounding microenvironment, which greatly influence cell functionality. Consequently, considerable efforts have been made to enhance in vitro models for drug development and disease research. Recently, microfluidic organ-on-a-chip systems have emerged as promising candidates to better mimic the dynamic nature of the BBB. This review provides a comprehensive overview of recent BBB-on-chip devices. The typical building blocks, chip designs, the perfusion infrastructure, and readouts used to characterize and evaluate BBB formation are presented, analyzed, and discussed in detail.</div></div><div><h3>Statement of Significance</h3><div>The blood-brain barrier (BBB) is a highly selective barrier that controls what can enter the brain. While it protects the brain from harmful substances, it also hinders the delivery of treatments for neurological diseases such as Alzheimer's and Parkinson's. Due to its complexity, studying the BBB in living organisms remains difficult. However, recent advances in “organ-on-a-chip” technology have allowed scientists to create small, engineered models that replicate the BBB. These models provide a powerful platform to study diseases and test potential drugs with greater accuracy than traditional methods. Organ-on-a-chip devices are designed to mimic the behavior of organs or tissues in the human body, offering a more realistic and controlled environment for research. This review highlights recent breakthroughs in BBB-on-a-chip technology, showing how these models enhance current research and have the potential to transform the way we study brain diseases and develop new drugs. By integrating biology and engineering, BBB-on-a-chip technology has the potential to transform neuroscience research, improve drug development, and enhance our understanding of brain disorders.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 1-28"},"PeriodicalIF":9.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702339","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
Early collagen degeneration in the temporomandibular intradiscal junction portends the onset of discal pathogenesis
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-21 DOI: 10.1016/j.actbio.2025.03.021
Jiahao Zhou , Liang Xie , Jie Zhang, Xinyi Deng, Haozhe Chen, Songsong Zhu, Nan Jiang
The temporomandibular intradiscal junction is a structural transition region connecting anteroposterior and circumferential aligned collagens fibers in the temporomandibular joint disc. Despite inherent stiffness, this region is incredibly susceptible to perforation under pathological conditions. This study aimed to determine whether the intradiscal junction was the initiation destructive site for discal degeneration. Utilizing high-resolution microscopy and nanoindentation, we characterized the structural and mechanical properties of the intradiscal junction. In rabbit models of anterior disc displacement-mediated temporomandibular osteoarthritis, we observed a significant reduction in collagen fibril diameter and an increase in denatured procollagen within the intradiscal junction as early as one week post-surgery, further spreading across the whole disc. Mass spectrometry proteomics showed that the alteration of the intradiscal junction was the consequence of mechanical stimuli mediated by tenascin-C and metalloproteinase-3. Notably, these degenerative changes were blocked by early reduction of the discal position. In vitro monotonic loading confirmed the dominant contribution of the intradiscal junction to the overall mechanical function of the disc. The present findings underscore the pivotal role of the intradiscal junction in the pathogenesis of discal degeneration, providing early detection indicators and therapeutics.

Statement of significance

Temporomandibular joint osteoarthritis (TMJOA) is a prevalent disorder affecting the structure and mechanics of the TMJ disc, with no effective early detection or treatment strategies. This study identifies the temporomandibular intradiscal junction (IJ) as the site where discal pathogenesis begins. Degeneration at the IJ involves reduced collagen fibril diameter and denatured procollagens, compromising the mechanical properties of the entire disc. Rescuing the IJ's position through TMJ anchorage surgery may restore mechanosensitive homeostasis and prevent further discal degeneration. These findings highlight the importance of the IJ in the discal progression, payving the way for early detection methods and treatment strategies that target aberrant remodeling in this critical region to slow or reverse disease.
{"title":"Early collagen degeneration in the temporomandibular intradiscal junction portends the onset of discal pathogenesis","authors":"Jiahao Zhou ,&nbsp;Liang Xie ,&nbsp;Jie Zhang,&nbsp;Xinyi Deng,&nbsp;Haozhe Chen,&nbsp;Songsong Zhu,&nbsp;Nan Jiang","doi":"10.1016/j.actbio.2025.03.021","DOIUrl":"10.1016/j.actbio.2025.03.021","url":null,"abstract":"<div><div>The temporomandibular intradiscal junction is a structural transition region connecting anteroposterior and circumferential aligned collagens fibers in the temporomandibular joint disc. Despite inherent stiffness, this region is incredibly susceptible to perforation under pathological conditions. This study aimed to determine whether the intradiscal junction was the initiation destructive site for discal degeneration. Utilizing high-resolution microscopy and nanoindentation, we characterized the structural and mechanical properties of the intradiscal junction. In rabbit models of anterior disc displacement-mediated temporomandibular osteoarthritis, we observed a significant reduction in collagen fibril diameter and an increase in denatured procollagen within the intradiscal junction as early as one week post-surgery, further spreading across the whole disc. Mass spectrometry proteomics showed that the alteration of the intradiscal junction was the consequence of mechanical stimuli mediated by tenascin-C and metalloproteinase-3. Notably, these degenerative changes were blocked by early reduction of the discal position. In vitro monotonic loading confirmed the dominant contribution of the intradiscal junction to the overall mechanical function of the disc. The present findings underscore the pivotal role of the intradiscal junction in the pathogenesis of discal degeneration, providing early detection indicators and therapeutics.</div></div><div><h3>Statement of significance</h3><div>Temporomandibular joint osteoarthritis (TMJOA) is a prevalent disorder affecting the structure and mechanics of the TMJ disc, with no effective early detection or treatment strategies. This study identifies the temporomandibular intradiscal junction (IJ) as the site where discal pathogenesis begins. Degeneration at the IJ involves reduced collagen fibril diameter and denatured procollagens, compromising the mechanical properties of the entire disc. Rescuing the IJ's position through TMJ anchorage surgery may restore mechanosensitive homeostasis and prevent further discal degeneration. These findings highlight the importance of the IJ in the discal progression, payving the way for early detection methods and treatment strategies that target aberrant remodeling in this critical region to slow or reverse disease.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 283-293"},"PeriodicalIF":9.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694777","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
Enhancing the biocompatibility of phakic intraocular lens via selective fibronectin trapping
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-21 DOI: 10.1016/j.actbio.2025.03.039
Yueze Hong , Jianyu Xin , Peng Wang , Yanhong Song , Xiangling Fan , Li Yang , Gaoyang Guo , Daihua Fu , Yan Dai , Fanjun Zhang , Yunbing Wang
Myopia has become a significant public health problem in recent decades, resulting in a profound public health and financial burden. The phakic intraocular lens (PIOL) utilized in myopia intraocular refractive surgery is constantly facing challenges in terms of uveal biocompatibility. Inspired by the “sandwich theory”, this study proposes the hypothesis that fibronectin (FN) can improve biocompatibility, and then creatively constructs a selective in-situ trap FN strategy. Specifically, PIOL surfaces with amide bonds covalently linking collagen were prepared, where selectivity was achieved by specific binding of collagen to FN. The obtained collagen modified material reduces immune response by reducing M1 polarization of macrophages, and its functionality and safety have been verified in vitro and in vivo. The grafting of collagen on the PIOL surface was able to occupy adsorption sites and inhibit the non-specific adsorption of other proteins while mimicking the extracellular matrix (ECM) microenvironment, further reducing the foreign body rejection. Overall, this strategy helps to address the issue of uveal biocompatibility in PIOL from a material design perspective, providing more economical and diversified options for patients with surgical needs.

Statement of significance

1. A phakic intraocular lens material with high ocular biocompatibility has been prepared. 2. By introducing acrylic anhydride and activating it, collagen is covalently grafted onto the surface of HEMA without altering its structure. 3. By utilizing the collagen binding domain in the structure of fibronectin, selective adsorption of fibronectin is enhanced, forming extracellular matrix analogs that reduce macrophage M1 polarization and lower inflammation.
{"title":"Enhancing the biocompatibility of phakic intraocular lens via selective fibronectin trapping","authors":"Yueze Hong ,&nbsp;Jianyu Xin ,&nbsp;Peng Wang ,&nbsp;Yanhong Song ,&nbsp;Xiangling Fan ,&nbsp;Li Yang ,&nbsp;Gaoyang Guo ,&nbsp;Daihua Fu ,&nbsp;Yan Dai ,&nbsp;Fanjun Zhang ,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2025.03.039","DOIUrl":"10.1016/j.actbio.2025.03.039","url":null,"abstract":"<div><div>Myopia has become a significant public health problem in recent decades, resulting in a profound public health and financial burden. The phakic intraocular lens (PIOL) utilized in myopia intraocular refractive surgery is constantly facing challenges in terms of uveal biocompatibility. Inspired by the “sandwich theory”, this study proposes the hypothesis that fibronectin (FN) can improve biocompatibility, and then creatively constructs a selective in-situ trap FN strategy. Specifically, PIOL surfaces with amide bonds covalently linking collagen were prepared, where selectivity was achieved by specific binding of collagen to FN. The obtained collagen modified material reduces immune response by reducing M1 polarization of macrophages, and its functionality and safety have been verified in vitro and in vivo. The grafting of collagen on the PIOL surface was able to occupy adsorption sites and inhibit the non-specific adsorption of other proteins while mimicking the extracellular matrix (ECM) microenvironment, further reducing the foreign body rejection. Overall, this strategy helps to address the issue of uveal biocompatibility in PIOL from a material design perspective, providing more economical and diversified options for patients with surgical needs.</div></div><div><h3>Statement of significance</h3><div>1. A phakic intraocular lens material with high ocular biocompatibility has been prepared. 2. By introducing acrylic anhydride and activating it, collagen is covalently grafted onto the surface of HEMA without altering its structure. 3. By utilizing the collagen binding domain in the structure of fibronectin, selective adsorption of fibronectin is enhanced, forming extracellular matrix analogs that reduce macrophage M1 polarization and lower inflammation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 240-255"},"PeriodicalIF":9.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694781","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 Peptide-Based Composite Hydrogel for Myocardial Infarction Treatment: ROS Scavenging and Angiogenesis Regulation
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-20 DOI: 10.1016/j.actbio.2025.03.035
Qiuhao Luo , Zhanshan Gao , Long Bai , Haolong Ye , Haonan Ye , Yue Wang , Yue Gao , Tianzi Chen , Haijin Chen , Yin Liu , Li Yang , Cheng Hu , Dongdong Wu , Yunbing Wang
After myocardial infarction (MI), the affected area of the myocardium falls into a state of ischemia and hypoxia, and subsequently, cardiomyocytes undergo a series of pathological changes and eventually transform into scar tissue. Therefore, restoring blood perfusion and reducing reactive oxygen species (ROS) are essential to promote the repair process of damaged myocardium. Here, the MMP12 (YWDAW) peptide which has a good antioxidant effect in deep-sea fish muscle, and the KRX (MRPYDANKR) peptide which shows a pro-angiogenesis effect from mammalian endothelial genes, were utilized collaboratively and loaded into an injectable GelMA hydrogel to achieve minimally invasive implantation and long-term retention at the MI site. The incorporation of bioactive peptides builds a stable and efficient system, which in addition to effectively removing ROS and promoting angiogenesis, avoids cell apoptosis and inflammation in the long run, and effectively inhibits the process of myocardial fibrosis. Both in vivo and in vitro experiments have shown that the combination of two short peptides with anti-oxidation and angiogenesis therapy can eventually achieve rapid repair of damaged myocardial tissue. This study fully demonstrated that natural functional peptides have great potential in promoting the repair and regeneration of infarcted hearts.

Statement of Significance

We have successfully synthesized antioxidant and pro-angiogenic peptides, which were subsequently incorporated into an injectable hydrogel matrix. This bioactive hydrogel system demonstrates dual therapeutic functions, effectively scavenging ROS while promoting angiogenesis, thereby facilitating cardiac tissue repair. Notably, the chemical synthesis approach employed in peptide production establishes a robust foundation for scalable manufacturing and broad biomedical applications, particularly in cardiovascular therapeutics.
{"title":"Bioactive Peptide-Based Composite Hydrogel for Myocardial Infarction Treatment: ROS Scavenging and Angiogenesis Regulation","authors":"Qiuhao Luo ,&nbsp;Zhanshan Gao ,&nbsp;Long Bai ,&nbsp;Haolong Ye ,&nbsp;Haonan Ye ,&nbsp;Yue Wang ,&nbsp;Yue Gao ,&nbsp;Tianzi Chen ,&nbsp;Haijin Chen ,&nbsp;Yin Liu ,&nbsp;Li Yang ,&nbsp;Cheng Hu ,&nbsp;Dongdong Wu ,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2025.03.035","DOIUrl":"10.1016/j.actbio.2025.03.035","url":null,"abstract":"<div><div>After myocardial infarction (MI), the affected area of the myocardium falls into a state of ischemia and hypoxia, and subsequently, cardiomyocytes undergo a series of pathological changes and eventually transform into scar tissue. Therefore, restoring blood perfusion and reducing reactive oxygen species (ROS) are essential to promote the repair process of damaged myocardium. Here, the MMP12 (YWDAW) peptide which has a good antioxidant effect in deep-sea fish muscle, and the KRX (MRPYDANKR) peptide which shows a pro-angiogenesis effect from mammalian endothelial genes, were utilized collaboratively and loaded into an injectable GelMA hydrogel to achieve minimally invasive implantation and long-term retention at the MI site. The incorporation of bioactive peptides builds a stable and efficient system, which in addition to effectively removing ROS and promoting angiogenesis, avoids cell apoptosis and inflammation in the long run, and effectively inhibits the process of myocardial fibrosis. Both <em>in vivo</em> and <em>in vitro</em> experiments have shown that the combination of two short peptides with anti-oxidation and angiogenesis therapy can eventually achieve rapid repair of damaged myocardial tissue. This study fully demonstrated that natural functional peptides have great potential in promoting the repair and regeneration of infarcted hearts.</div></div><div><h3>Statement of Significance</h3><div>We have successfully synthesized antioxidant and pro-angiogenic peptides, which were subsequently incorporated into an injectable hydrogel matrix. This bioactive hydrogel system demonstrates dual therapeutic functions, effectively scavenging ROS while promoting angiogenesis, thereby facilitating cardiac tissue repair. Notably, the chemical synthesis approach employed in peptide production establishes a robust foundation for scalable manufacturing and broad biomedical applications, particularly in cardiovascular therapeutics.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 167-183"},"PeriodicalIF":9.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694769","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
Construction of anti-calcification small-diameter vascular grafts using decellularized extracellular matrix/poly (L-lactide-co-ε-caprolactone) and baicalin-cathepsin S inhibitor
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-20 DOI: 10.1016/j.actbio.2025.03.033
Yanjiao Teng , Xiaohai Zhang , Lin Song , Jianing Yang , Duo Li , Ziqi Shi , Xiaoqin Guo , Shufang Wang , Haojun Fan , Li Jiang , Shike Hou , Seeram Ramakrishna , Qi Lv , Jie Shi
The long-term transplantation of small-diameter vascular grafts (SDVGs) is associated with a risk of calcification, which is a key factor limiting the clinical translation of SDVG. Hence, there is an urgency attached to the development of new SDVGs with anti-calcification properties. Here, we used decellularized extracellular matrix (dECM) and poly (L-lactide-co-ε-caprolactone) (PLCL) as base materials and combined these with baicalin, cathepsin S (Cat S) inhibitor to prepare PBC-SDVGs by electrospinning. Baicalin contains carboxyl and hydroxyl groups that can interact with chemical groups in dECM powder, potentially blocking calcium nucleation sites. Cat S inhibitor prevents elastin degradation and further reduces the risk of calcification. PBC-SDVGs were biocompatible and when implanted in rat abdominal aorta, accelerated endothelialization, enhanced vascular tissue regeneration, inhibited elastin degradation, and promoted macrophage polarization M2 phenotype to regulate inflammation. After 3 months of implantation, the results of Doppler ultrasound, MicroCT, and histological staining revealed a significant reduction in calcification. In summary, the developed anti-calcification SDVGs offer a promising strategy for long-term implantation with significant clinical application potential.

Statement of Significance

The dECM and PLCL were used as base materials, connected with baicalin, and loaded with Cat S inhibitor to prepare PBC-SDVGs. The baicalin and dECM powder formed hydrogen bonds to crosslink together reducing the calcium deposition. In vitro, the vascular graft downregulated the expression level of osteogenic genes and promoted macrophage polarization toward an anti-inflammatory M2 phenotype, thereby reducing calcification. The PBC-SDVGs implanted in rat abdominal aorta can accelerate endothelialization, enhance vascular tissue regeneration, inhibit elastin degradation, reduce inflammation response and calcification.
{"title":"Construction of anti-calcification small-diameter vascular grafts using decellularized extracellular matrix/poly (L-lactide-co-ε-caprolactone) and baicalin-cathepsin S inhibitor","authors":"Yanjiao Teng ,&nbsp;Xiaohai Zhang ,&nbsp;Lin Song ,&nbsp;Jianing Yang ,&nbsp;Duo Li ,&nbsp;Ziqi Shi ,&nbsp;Xiaoqin Guo ,&nbsp;Shufang Wang ,&nbsp;Haojun Fan ,&nbsp;Li Jiang ,&nbsp;Shike Hou ,&nbsp;Seeram Ramakrishna ,&nbsp;Qi Lv ,&nbsp;Jie Shi","doi":"10.1016/j.actbio.2025.03.033","DOIUrl":"10.1016/j.actbio.2025.03.033","url":null,"abstract":"<div><div>The long-term transplantation of small-diameter vascular grafts (SDVGs) is associated with a risk of calcification, which is a key factor limiting the clinical translation of SDVG. Hence, there is an urgency attached to the development of new SDVGs with anti-calcification properties. Here, we used decellularized extracellular matrix (dECM) and poly (L-lactide-co-ε-caprolactone) (PLCL) as base materials and combined these with baicalin, cathepsin S (Cat S) inhibitor to prepare PBC-SDVGs by electrospinning. Baicalin contains carboxyl and hydroxyl groups that can interact with chemical groups in dECM powder, potentially blocking calcium nucleation sites. Cat S inhibitor prevents elastin degradation and further reduces the risk of calcification. PBC-SDVGs were biocompatible and when implanted in rat abdominal aorta, accelerated endothelialization, enhanced vascular tissue regeneration, inhibited elastin degradation, and promoted macrophage polarization M2 phenotype to regulate inflammation. After 3 months of implantation, the results of Doppler ultrasound, MicroCT, and histological staining revealed a significant reduction in calcification. In summary, the developed anti-calcification SDVGs offer a promising strategy for long-term implantation with significant clinical application potential.</div></div><div><h3>Statement of Significance</h3><div>The dECM and PLCL were used as base materials, connected with baicalin, and loaded with Cat S inhibitor to prepare PBC-SDVGs. The baicalin and dECM powder formed hydrogen bonds to crosslink together reducing the calcium deposition. <em>In vitro</em>, the vascular graft downregulated the expression level of osteogenic genes and promoted macrophage polarization toward an anti-inflammatory M2 phenotype, thereby reducing calcification. The PBC-SDVGs implanted in rat abdominal aorta can accelerate endothelialization, enhance vascular tissue regeneration, inhibit elastin degradation, reduce inflammation response and calcification.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 184-201"},"PeriodicalIF":9.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694771","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
Modulating biomechanical and integrating biochemical cues to foster adaptive remodeling of tissue engineered matrices for cardiovascular implants 调节生物力学并整合生物化学线索,促进心血管植入物组织工程基质的适应性重塑。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-19 DOI: 10.1016/j.actbio.2025.03.036
Pascal Breitenstein , Valery L. Visser , Sarah E. Motta , Marcy Martin , Melanie Generali , Frank P.T. Baaijens , Sandra Loerakker , Christopher K. Breuer , Simon P. Hoerstrup , Maximilian Y. Emmert
Cardiovascular disease remains one of the leading causes of mortality in the Western world. Congenital heart disease affects nearly 1 % of newborns, with approximately one-fourth requiring reconstructive surgery during their lifetime. Current cardiovascular replacement options have significant limitations. Their inability to grow poses particular challenges for pediatric patients. Tissue Engineered Matrix (TEM)-based in situ constructs, with their self-repair and growth potential, offer a promising solution to overcome the limitations of current clinically used replacement options. Various functionalization strategies, involving the integration of biomechanical or biochemical components to enhance biocompatibility, have been developed for Tissue Engineered Vascular Grafts (TEVG) and Tissue Engineered Heart Valves (TEHV) to foster their capacity for in vivo remodeling. In this review, we present the current state of clinical translation for TEVG and TEHV, and provide a comprehensive overview of biomechanical and biochemical functionalization strategies for TEVG and TEHV. We discuss the rationale for functionalization, the implementation of functionalization cues in TEM-based TEVG and TEHV, and the interrelatedness of biomechanical and biochemical cues in the in vivo response. Finally, we address the challenges associated with functionalization and discuss how interdisciplinary research, especially when combined with in silico models, could enhance the translation of these strategies into clinical applications.

Statement of significance

Cardiovascular disease remains one of the leading causes of mortality, with current replacements being unable to grow and regenerate. In this review, we present the current state of clinical translation for tissue engineered vascular grafts (TEVG) and heart valves (TEHV). Particularly, we discuss the rationale and implementation for functionalization cues in tissue engineered matrix-based TEVGs and TEHVs, and for the first time we introduce the interrelatedness of biomechanical and biochemical cues in the in-vivo response. These insights pave the way for next-generation cardiovascular implants that promise better durability, biocompatibility, and growth potential. Finally, we address the challenges associated with functionalization and discuss how interdisciplinary research, especially when combined with in silico models, could enhance the translation of these strategies into clinical applications .
{"title":"Modulating biomechanical and integrating biochemical cues to foster adaptive remodeling of tissue engineered matrices for cardiovascular implants","authors":"Pascal Breitenstein ,&nbsp;Valery L. Visser ,&nbsp;Sarah E. Motta ,&nbsp;Marcy Martin ,&nbsp;Melanie Generali ,&nbsp;Frank P.T. Baaijens ,&nbsp;Sandra Loerakker ,&nbsp;Christopher K. Breuer ,&nbsp;Simon P. Hoerstrup ,&nbsp;Maximilian Y. Emmert","doi":"10.1016/j.actbio.2025.03.036","DOIUrl":"10.1016/j.actbio.2025.03.036","url":null,"abstract":"<div><div>Cardiovascular disease remains one of the leading causes of mortality in the Western world. Congenital heart disease affects nearly 1 % of newborns, with approximately one-fourth requiring reconstructive surgery during their lifetime. Current cardiovascular replacement options have significant limitations. Their inability to grow poses particular challenges for pediatric patients. Tissue Engineered Matrix (TEM)-based <em>in situ</em> constructs, with their self-repair and growth potential, offer a promising solution to overcome the limitations of current clinically used replacement options. Various functionalization strategies, involving the integration of biomechanical or biochemical components to enhance biocompatibility, have been developed for Tissue Engineered Vascular Grafts (TEVG) and Tissue Engineered Heart Valves (TEHV) to foster their capacity for <em>in vivo</em> remodeling. In this review, we present the current state of clinical translation for TEVG and TEHV, and provide a comprehensive overview of biomechanical and biochemical functionalization strategies for TEVG and TEHV. We discuss the rationale for functionalization, the implementation of functionalization cues in TEM-based TEVG and TEHV, and the interrelatedness of biomechanical and biochemical cues in the <em>in vivo</em> response. Finally, we address the challenges associated with functionalization and discuss how interdisciplinary research, especially when combined with <em>in silico</em> models, could enhance the translation of these strategies into clinical applications.</div></div><div><h3>Statement of significance</h3><div>Cardiovascular disease remains one of the leading causes of mortality, with current replacements being unable to grow and regenerate. In this review, we present the current state of clinical translation for tissue engineered vascular grafts (TEVG) and heart valves (TEHV). Particularly, we discuss the rationale and implementation for functionalization cues in tissue engineered matrix-based TEVGs and TEHVs, and for the first time we introduce the interrelatedness of biomechanical and biochemical cues in the <em>in-vivo</em> response. These insights pave the way for next-generation cardiovascular implants that promise better durability, biocompatibility, and growth potential. Finally, we address the challenges associated with functionalization and discuss how interdisciplinary research, especially when combined with <em>in silico</em> models, could enhance the translation of these strategies into clinical applications .</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 48-67"},"PeriodicalIF":9.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675034","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
Osteogenic surgical sutures for tendon traction and fixation: A model of achilles tendon sleeve avulsion 用于肌腱牵引和固定的成骨缝合线:跟腱套撕脱模型。
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-19 DOI: 10.1016/j.actbio.2025.03.037
Xiao Yu , Genbin Wu , Yangfan Ding , Panpan Shang , Pengfei Cai , Jie Cui , Jiahui Song , Jinglei Wu , Mohamed EL-Newehy , Meera Moydeen Abdulhameed , Xiumei Mo , Yinxian Yu , Binbin Sun
Currently, the repair of Achilles tendon sleeve avulsion is a challenge due to their limited research and particularly difficult treatment. In tendon repair surgery, the construction of bone tunnels is required for the suspensory fixation of ruptured tendon by sutures. However, due to the biologically inert of commonly used tendon sutures, postoperative fixation instability, bone tunnel enlargement, and even tendon reconstruction failure can easily occur under stressful conditions. In this study, core-spun nanoyarns containing β-tricalcium phosphate (β-TCP) were prepared by electrospinning to serve as surgical sutures for tendon traction and fixation. The suture of 6 core-spun nanoyarns spun again into one strand had stronger mechanical properties, which could effectively pull the tendon. The silk fibroin micron yarn of the suture core layer and the polycaprolactone/silk fibroin/β-TCP nanofibers of the shell layer demonstrated favorable biocompatibility, which facilitated cell adhesion and expression in the tendon and bone. In the repair surgery of the Achilles tendon sleeve avulsion in rabbits, compared with non-degradable and high mechanical properties commercial sutures, the β-TCP in the nanofibers of sutures could induce osteogenesis, thereby reducing the gap in the bone tunnel and preventing enlargement of the bone tunnel. In conclusion, the suture could weave the ruptured tendon, fix the tendon to the bone, promote the formation of new bone in the bone tunnel, avoid the instability of the existing commercial sutures to the bone tunnel, and ultimately improve the success rate of tendon repair surgery.

Statement of Significance

Nowadays, there is very limited research on the Achilles tendon sleeve avulsion model. This model presents challenges due to inadequate tendon tissue in the calcaneus for direct repair and insufficient bone tissue on the avulsed tendon for fixation. The incidence of this model is low, but treatment once it occurs is particularly difficult. In this study, we proposed to compound osteogenesis-promoting β-TCP materials onto nanoyarns to prepare surgical sutures that could weave the ruptured tendon, fix the tendon to the bone, induce osteogenesis, and reduce the gap in the bone tunnel, thus avoiding the instability of the existing commercial sutures in the bone tunnel, and ultimately improving the success rate of the surgery.
{"title":"Osteogenic surgical sutures for tendon traction and fixation: A model of achilles tendon sleeve avulsion","authors":"Xiao Yu ,&nbsp;Genbin Wu ,&nbsp;Yangfan Ding ,&nbsp;Panpan Shang ,&nbsp;Pengfei Cai ,&nbsp;Jie Cui ,&nbsp;Jiahui Song ,&nbsp;Jinglei Wu ,&nbsp;Mohamed EL-Newehy ,&nbsp;Meera Moydeen Abdulhameed ,&nbsp;Xiumei Mo ,&nbsp;Yinxian Yu ,&nbsp;Binbin Sun","doi":"10.1016/j.actbio.2025.03.037","DOIUrl":"10.1016/j.actbio.2025.03.037","url":null,"abstract":"<div><div>Currently, the repair of Achilles tendon sleeve avulsion is a challenge due to their limited research and particularly difficult treatment. In tendon repair surgery, the construction of bone tunnels is required for the suspensory fixation of ruptured tendon by sutures. However, due to the biologically inert of commonly used tendon sutures, postoperative fixation instability, bone tunnel enlargement, and even tendon reconstruction failure can easily occur under stressful conditions. In this study, core-spun nanoyarns containing β-tricalcium phosphate (β-TCP) were prepared by electrospinning to serve as surgical sutures for tendon traction and fixation. The suture of 6 core-spun nanoyarns spun again into one strand had stronger mechanical properties, which could effectively pull the tendon. The silk fibroin micron yarn of the suture core layer and the polycaprolactone/silk fibroin/β-TCP nanofibers of the shell layer demonstrated favorable biocompatibility, which facilitated cell adhesion and expression in the tendon and bone. In the repair surgery of the Achilles tendon sleeve avulsion in rabbits, compared with non-degradable and high mechanical properties commercial sutures, the β-TCP in the nanofibers of sutures could induce osteogenesis, thereby reducing the gap in the bone tunnel and preventing enlargement of the bone tunnel. In conclusion, the suture could weave the ruptured tendon, fix the tendon to the bone, promote the formation of new bone in the bone tunnel, avoid the instability of the existing commercial sutures to the bone tunnel, and ultimately improve the success rate of tendon repair surgery.</div></div><div><h3>Statement of Significance</h3><div>Nowadays, there is very limited research on the Achilles tendon sleeve avulsion model. This model presents challenges due to inadequate tendon tissue in the calcaneus for direct repair and insufficient bone tissue on the avulsed tendon for fixation. The incidence of this model is low, but treatment once it occurs is particularly difficult. In this study, we proposed to compound osteogenesis-promoting β-TCP materials onto nanoyarns to prepare surgical sutures that could weave the ruptured tendon, fix the tendon to the bone, induce osteogenesis, and reduce the gap in the bone tunnel, thus avoiding the instability of the existing commercial sutures in the bone tunnel, and ultimately improving the success rate of the surgery.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 202-215"},"PeriodicalIF":9.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675037","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
pH-responsive photothermal effect and heterojunction formation for tumor-specific pyroelectrodynamic and nanozyme-catalyzed starvation therapy
IF 9.4 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-03-18 DOI: 10.1016/j.actbio.2025.03.031
Xia Lei , Jie Meng , Tianyu Gao, Mengxue Zhang, Zhanlin Zhang, Shuang Xie, Yupeng Su, Xiaohong Li
<div><div>Pyroelectrodynamic therapy (PEDT) integrates photothermal ablation and catalytic generation of reactive oxygen species (ROS), yet tumor-specific PEDT remains unexplored. Herein, pyroelectric tetragonal BaTiO<sub>3</sub> (tBT) nanoparticles (NPs) were capped with polyaniline (PANI) via a Pickering emulsion-masking method, followed by in situ deposition of MnO<sub>2</sub> nanodots on PANI caps to synthesize Janus tBT@PANI-MnO<sub>2</sub> NPs. PANI emeraldine salts (PANI-ES) at pH 6.5 display strong near-infrared II (NIR-II) absorption and 4.67-fold higher photothermal conversion efficiency than that of PANI emeraldine base at pH 7.4. MnO<sub>2</sub> nanodots exhibit self-propagating glucose oxidase (GOx), peroxidase (POD), and catalase (CAT) catalytic activities, remodeling the tumor microenvironment and enhancing PTT and PEDT efficacy. Heterojunction formation with PANI-ES generates 1.63-fold higher pyroelectric potentials compared to pristine tBT NPs. The pyroelectric field selectively alters tumor cell membrane potential and, along with the self-propelled motion by asymmetrical thermophoresis from the Janus structure, promotes cellular uptake of NPs. Tumor accumulation of NPs increases 3.2 folds with broad intratumoral distributions of NPs and ROS. Synergistic toxicities to tumor cells arise from PANI-mediated photothermal effect, ROS generation from tBT-PANI heterojunctions, and MnO<sub>2</sub> nanozymes-catalyzed glucose depletion. Integration of PEDT, mild PTT and MnO<sub>2</sub>-catalyzed starvation therapy completely inhibits tumor growth, extends animal survival, elevated intratumoral O<sub>2</sub> levels, and suppressed adenosine triphosphate productions. Thus, this Janus NP design represents the first attempt to develop pH-responsive heterojunctions and enables tumor-specific PTT, PEDT and nanozyme-catalyzed starvation therapy.</div></div><div><h3>Statement of significance</h3><div>Although phototherapy achieves light localization for tumor suppression, inevitable toxicities usually occur when light penetrates healthy tissues with accumulation of photoactive agents. Extensive efforts have been dedicated to exploring tumor microenvironment-responsive drug delivery systems, aiming to enhance tumor-targeting efficiency and treatment selectivity of anticancer agents. However, to date, no efforts have been made to develop a method that can achieve tumor-specific temperature elevation and pyroelectrodynamic therapy while simultaneously minimizing exposure to normal tissues. To address these challenges, a concise strategy is proposed to generate pyroelectric heterojunctions in response to the slightly acidic tumor microenvironment, taking advantages of reversible protonation and deprotonation properties of polyaniline. The tumor-specific conversion into polyaniline emeraldine salts triggers strong NIR-II absorptions and pyroelectric effect, and the self-propagated catalytic reactions of MnO<sub>2</sub> nanozymes reinforce photothermal
热释电动力疗法(PEDT)集光热消融和催化反应性氧(ROS)生成于一体,但针对肿瘤的热释电动力疗法仍有待探索。在此,通过皮克林乳液掩蔽法将热释电四边形 BaTiO3(tBT)纳米粒子(NPs)与聚苯胺(PANI)封端,然后在 PANI 封端原位沉积 MnO2 纳米点,合成了 Janus tBT@PANI-MnO2 NPs。与 pH 值为 7.4 的 PANI 绿宝石碱相比,pH 值为 6.5 的 PANI 绿宝石盐(PANI-ES)具有较强的近红外 II(NIR-II)吸收,光热转换效率高 4.67 倍。MnO2 纳米点具有自增葡萄糖氧化酶(GOx)、过氧化物酶(POD)和过氧化氢酶(CAT)催化活性,可重塑肿瘤微环境并提高 PTT 和 PEDT 的疗效。与原始 tBT NPs 相比,与 PANI-ES 形成的异质结产生的热电势高出 1.63 倍。热电场可选择性地改变肿瘤细胞膜电位,再加上 Janus 结构的非对称热泳自推动运动,促进了细胞对 NPs 的吸收。随着 NPs 和 ROS 在肿瘤内的广泛分布,NPs 的肿瘤积累增加了 3.2 倍。PANI 介导的光热效应、tBT-PANI 异质结产生的 ROS 以及 MnO2 纳米酶催化的葡萄糖耗竭对肿瘤细胞产生了协同毒性。整合 PEDT、温和 PTT 和 MnO2 催化的饥饿疗法可完全抑制肿瘤生长、延长动物存活期、提高瘤内氧气水平并抑制三磷酸腺苷的生成。因此,这种 Janus NP 设计是开发 pH 响应异质结的首次尝试,可实现肿瘤特异性 PTT、PEDT 和纳米酶催化饥饿疗法。意义说明:虽然光疗实现了光定位以抑制肿瘤,但当光穿透健康组织并积累光活性剂时,通常会产生不可避免的毒性。人们一直致力于探索肿瘤微环境响应型给药系统,旨在提高抗癌药物的肿瘤靶向效率和治疗选择性。然而,迄今为止,人们还没有努力开发出一种方法,既能实现肿瘤特异性升温和热释电治疗,又能最大限度地减少对正常组织的暴露。为了应对这些挑战,我们提出了一种简洁的策略,利用聚苯胺的可逆质子化和去质子化特性,针对微酸性肿瘤微环境生成热释电异质结。肿瘤特异性转化为聚苯胺祖母绿盐会引发强烈的近红外-II吸收和热释电效应,MnO2纳米酶的自促进催化反应会加强肿瘤的光热、热释电和饥饿疗法。
{"title":"pH-responsive photothermal effect and heterojunction formation for tumor-specific pyroelectrodynamic and nanozyme-catalyzed starvation therapy","authors":"Xia Lei ,&nbsp;Jie Meng ,&nbsp;Tianyu Gao,&nbsp;Mengxue Zhang,&nbsp;Zhanlin Zhang,&nbsp;Shuang Xie,&nbsp;Yupeng Su,&nbsp;Xiaohong Li","doi":"10.1016/j.actbio.2025.03.031","DOIUrl":"10.1016/j.actbio.2025.03.031","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Pyroelectrodynamic therapy (PEDT) integrates photothermal ablation and catalytic generation of reactive oxygen species (ROS), yet tumor-specific PEDT remains unexplored. Herein, pyroelectric tetragonal BaTiO&lt;sub&gt;3&lt;/sub&gt; (tBT) nanoparticles (NPs) were capped with polyaniline (PANI) via a Pickering emulsion-masking method, followed by in situ deposition of MnO&lt;sub&gt;2&lt;/sub&gt; nanodots on PANI caps to synthesize Janus tBT@PANI-MnO&lt;sub&gt;2&lt;/sub&gt; NPs. PANI emeraldine salts (PANI-ES) at pH 6.5 display strong near-infrared II (NIR-II) absorption and 4.67-fold higher photothermal conversion efficiency than that of PANI emeraldine base at pH 7.4. MnO&lt;sub&gt;2&lt;/sub&gt; nanodots exhibit self-propagating glucose oxidase (GOx), peroxidase (POD), and catalase (CAT) catalytic activities, remodeling the tumor microenvironment and enhancing PTT and PEDT efficacy. Heterojunction formation with PANI-ES generates 1.63-fold higher pyroelectric potentials compared to pristine tBT NPs. The pyroelectric field selectively alters tumor cell membrane potential and, along with the self-propelled motion by asymmetrical thermophoresis from the Janus structure, promotes cellular uptake of NPs. Tumor accumulation of NPs increases 3.2 folds with broad intratumoral distributions of NPs and ROS. Synergistic toxicities to tumor cells arise from PANI-mediated photothermal effect, ROS generation from tBT-PANI heterojunctions, and MnO&lt;sub&gt;2&lt;/sub&gt; nanozymes-catalyzed glucose depletion. Integration of PEDT, mild PTT and MnO&lt;sub&gt;2&lt;/sub&gt;-catalyzed starvation therapy completely inhibits tumor growth, extends animal survival, elevated intratumoral O&lt;sub&gt;2&lt;/sub&gt; levels, and suppressed adenosine triphosphate productions. Thus, this Janus NP design represents the first attempt to develop pH-responsive heterojunctions and enables tumor-specific PTT, PEDT and nanozyme-catalyzed starvation therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Although phototherapy achieves light localization for tumor suppression, inevitable toxicities usually occur when light penetrates healthy tissues with accumulation of photoactive agents. Extensive efforts have been dedicated to exploring tumor microenvironment-responsive drug delivery systems, aiming to enhance tumor-targeting efficiency and treatment selectivity of anticancer agents. However, to date, no efforts have been made to develop a method that can achieve tumor-specific temperature elevation and pyroelectrodynamic therapy while simultaneously minimizing exposure to normal tissues. To address these challenges, a concise strategy is proposed to generate pyroelectric heterojunctions in response to the slightly acidic tumor microenvironment, taking advantages of reversible protonation and deprotonation properties of polyaniline. The tumor-specific conversion into polyaniline emeraldine salts triggers strong NIR-II absorptions and pyroelectric effect, and the self-propagated catalytic reactions of MnO&lt;sub&gt;2&lt;/sub&gt; nanozymes reinforce photothermal","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 444-459"},"PeriodicalIF":9.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672012","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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