Biomaterials最新文献_第3页

Nanozyme-functionalized microalgal biohybrid microrobots in inflammatory bowel disease treatment

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-01 DOI: 10.1016/j.biomaterials.2025.123231

Jinmei Yang , Jiamin Ye , Runtan Li , Ruiyan Li , Xinting Liu , Jingwen Han , Yiwen Yang , Nana Ran , Mengyu Yuan , Zhuhong Zhang , Wei Chong , Xiaoyuan Ji

Oral drugs are the most direct and effective strategy for the treatment of gastrointestinal diseases. However, the harsh environment of gastric juice, lack of targeted lesion sites, and rapid metabolism present difficulties in the development of oral drugs. This research introduces a nanozyme-functionalized microalgal biohybrid microrobot (Hp@CS-PNAs@PAA) with a novel mechanism for treating inflammatory bowel disease (IBD) by leveraging the therapeutic advantages of microalgae and nanozymes. The microrobot uniquely combines the natural antioxidant capacity of Hematococcus pluvialis (Hp) microalgae and the catalytically active enzyme-mimicking properties of platinum-based nanoparticle assemblies (PNAs), enabling enhanced scavenging of reactive oxygen species (ROS) and targeted anti-inflammatory effects. Through its layered design, the Hp@CS-PNAs@PAA microrobot can navigate the gastrointestinal tract, resist degradation, and target inflamed colon tissues via electrostatic interactions, achieving extended retention and prolonged therapeutic action at inflammation sites. This study demonstrated that the synergistic anti-inflammatory effects of the microrobot derive from its ability to reduce ROS, inhibit proinflammatory cytokines, and promote the expression of tight junction proteins critical for preserving the integrity of the intestinal barrier. Both in vitro and in vivo tests in a DSS-induced colitis mouse model revealed that this system effectively restores damaged tissues by reducing oxidative stress and inflammation, indicating significant potential for clinical application in the management of colitis and similar inflammatory diseases.

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引用次数: 0

Overcoming immunotherapy resistance in colorectal cancer through nano-selenium probiotic complexes and IL-32 modulation

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-01 DOI: 10.1016/j.biomaterials.2025.123233

Shiquan Li, Tao Liu, Chenyao Li, Zhiyuan Zhang, Jiantao Zhang, Di Sun

Background and objective

Colorectal cancer (CRC) is a major global health burden, with immunotherapy often limited by immune tolerance and resistance. This study introduces an innovative approach using Selenium Nanoparticles-Loaded Extracellular Vesicles combined with Interleukin-32 and Engineered Probiotic Escherichia coli Nissle 1917 (SeNVs@NE-IL32-EcN) to enhance CD8⁺ T cell-mediated immune responses and overcome immunotherapy resistance.

Methods

Single-cell RNA sequencing (scRNA-seq) and transcriptomic analyses were performed to identify key immune cells and regulators involved in CRC immunotherapy resistance, focusing on CD8⁺ T cells and the regulatory factor IL32. A humanized xenograft mouse model was used to evaluate the impact of IL32 and SeNVs@NE-IL32-EcN on tumor growth and immune responses. The SeNVs@NE-IL32-EcN complex was synthesized through a reverse micelle method and functionalized using extracellular vesicles. Its morphology, size, antioxidant activity, and safety were characterized using electron microscopy, dynamic light scattering (DLS), and in vitro co-culture assays.

Results

Single-cell analyses revealed a significant reduction in CD8⁺ T cell infiltration in immunotherapy-resistant CRC patients. IL32 was identified as a key regulator enhancing CD8⁺ T cell cytotoxic activity through granzyme B and IFN-γ secretion. Treatment with SeNVs@NE-IL32-EcN significantly improved the proliferation and activity of CD8⁺ T cells and reduced tumor progression in humanized mouse models. In vitro and in vivo results demonstrated the complex's biocompatibility, antioxidant properties, and ability to enhance CRC immunotherapy while mitigating immune tolerance.

Conclusion

SeNVs@NE-IL32-EcN offers a novel nano-biomaterial strategy that integrates nanotechnology and probiotic therapy to enhance CD8⁺ T cell-mediated immunity and overcome CRC immunotherapy resistance. This study lays the foundation for future therapeutic applications in cancer treatment by advancing immune-modulating biomaterials.

{"title":"Overcoming immunotherapy resistance in colorectal cancer through nano-selenium probiotic complexes and IL-32 modulation","authors":"Shiquan Li, Tao Liu, Chenyao Li, Zhiyuan Zhang, Jiantao Zhang, Di Sun","doi":"10.1016/j.biomaterials.2025.123233","DOIUrl":"10.1016/j.biomaterials.2025.123233","url":null,"abstract":"<div><h3>Background and objective</h3><div>Colorectal cancer (CRC) is a major global health burden, with immunotherapy often limited by immune tolerance and resistance. This study introduces an innovative approach using Selenium Nanoparticles-Loaded Extracellular Vesicles combined with Interleukin-32 and Engineered Probiotic <em>Escherichia coli</em> Nissle 1917 (SeNVs@NE-IL32-EcN) to enhance CD8<sup>+</sup> T cell-mediated immune responses and overcome immunotherapy resistance.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing (scRNA-seq) and transcriptomic analyses were performed to identify key immune cells and regulators involved in CRC immunotherapy resistance, focusing on CD8<sup>+</sup> T cells and the regulatory factor IL32. A humanized xenograft mouse model was used to evaluate the impact of IL32 and SeNVs@NE-IL32-EcN on tumor growth and immune responses. The SeNVs@NE-IL32-EcN complex was synthesized through a reverse micelle method and functionalized using extracellular vesicles. Its morphology, size, antioxidant activity, and safety were characterized using electron microscopy, dynamic light scattering (DLS), and <em>in vitro</em> co-culture assays.</div></div><div><h3>Results</h3><div>Single-cell analyses revealed a significant reduction in CD8<sup>+</sup> T cell infiltration in immunotherapy-resistant CRC patients. IL32 was identified as a key regulator enhancing CD8<sup>+</sup> T cell cytotoxic activity through granzyme B and IFN-γ secretion. Treatment with SeNVs@NE-IL32-EcN significantly improved the proliferation and activity of CD8<sup>+</sup> T cells and reduced tumor progression in humanized mouse models. <em>In vitro</em> and <em>in vivo</em> results demonstrated the complex's biocompatibility, antioxidant properties, and ability to enhance CRC immunotherapy while mitigating immune tolerance.</div></div><div><h3>Conclusion</h3><div>SeNVs@NE-IL32-EcN offers a novel nano-biomaterial strategy that integrates nanotechnology and probiotic therapy to enhance CD8<sup>+</sup> T cell-mediated immunity and overcome CRC immunotherapy resistance. This study lays the foundation for future therapeutic applications in cancer treatment by advancing immune-modulating biomaterials.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123233"},"PeriodicalIF":12.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601136","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

Acidity-unlocked glucose oxidase as drug vector to boost intratumor copper homeostatic imbalance-enhanced cuproptosis for metastasis inhibition and anti-tumor immunity

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-28 DOI: 10.1016/j.biomaterials.2025.123207

Junrong Wang, Yulin Xie, Guoqing Zhu, Yanrong Qian, Qianqian Sun, Haoze Li, Chunxia Li

As one of the key tools of biocatalysis, natural enzymes have received extensive attention due to their unique activity. However, the non-selective catalysis and early leakage induced by delivery dependency of natural enzymes can cause side effects on normal tissues. Moreover, although cuproptosis is an emerging tumor-inhibiting programmed cell death, the occurrence of cuproptosis leads to high expression of Cu-dependent lysyl oxidase-like 2 (LOXL2), which promotes tumor metastasis. Herein, in order to intelligently regulate the “OFF-to-ON” catalytic activity of glucose oxidase (a natural enzyme called GOx) and simultaneously inhibit tumor metastasis caused by Cu imbalance, an acidity-unlocked GOx system drug carrier was constructed by co-assembling Cu ions and omeprazole (OPZ) on GOx exposing sulfhydryl and hydrophobic pockets. The GOx activity is significantly inhibited due to the coordination of Cu ions with sulfhydryl groups and the interaction of hydrophobic small molecule OPZ with hydrophobic bags, which results in specificity for tumor cells and ensures the safety of GOx in blood circulation. Meanwhile, dysregulation of intracellular Cu homeostasis that impairs the Cu-dependence of LOXL2 not only inhibits critical signaling during epithelial-mesenchymal transformation (EMT) and extracellular matrix (ECM) remodelling to prevent tumor metastasis, but also exacerbates enhanced cuproptosis induced by tumor metabolic stress, thereby reversing the immunosuppressive microenvironment. This strategy of acidity-unlocked the catalytic function of natural enzymes and LOXL2 activity inhibition provides a novel option for enhancing cuproptosis to inhibit tumor metastasis and anti-tumor immunity.

{"title":"Acidity-unlocked glucose oxidase as drug vector to boost intratumor copper homeostatic imbalance-enhanced cuproptosis for metastasis inhibition and anti-tumor immunity","authors":"Junrong Wang, Yulin Xie, Guoqing Zhu, Yanrong Qian, Qianqian Sun, Haoze Li, Chunxia Li","doi":"10.1016/j.biomaterials.2025.123207","DOIUrl":"10.1016/j.biomaterials.2025.123207","url":null,"abstract":"<div><div>As one of the key tools of biocatalysis, natural enzymes have received extensive attention due to their unique activity. However, the non-selective catalysis and early leakage induced by delivery dependency of natural enzymes can cause side effects on normal tissues. Moreover, although cuproptosis is an emerging tumor-inhibiting programmed cell death, the occurrence of cuproptosis leads to high expression of Cu-dependent lysyl oxidase-like 2 (LOXL2), which promotes tumor metastasis. Herein, in order to intelligently regulate the “OFF-to-ON” catalytic activity of glucose oxidase (a natural enzyme called GOx) and simultaneously inhibit tumor metastasis caused by Cu imbalance, an acidity-unlocked GOx system drug carrier was constructed by co-assembling Cu ions and omeprazole (OPZ) on GOx exposing sulfhydryl and hydrophobic pockets. The GOx activity is significantly inhibited due to the coordination of Cu ions with sulfhydryl groups and the interaction of hydrophobic small molecule OPZ with hydrophobic bags, which results in specificity for tumor cells and ensures the safety of GOx in blood circulation. Meanwhile, dysregulation of intracellular Cu homeostasis that impairs the Cu-dependence of LOXL2 not only inhibits critical signaling during epithelial-mesenchymal transformation (EMT) and extracellular matrix (ECM) remodelling to prevent tumor metastasis, but also exacerbates enhanced cuproptosis induced by tumor metabolic stress, thereby reversing the immunosuppressive microenvironment. This strategy of acidity-unlocked the catalytic function of natural enzymes and LOXL2 activity inhibition provides a novel option for enhancing cuproptosis to inhibit tumor metastasis and anti-tumor immunity.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123207"},"PeriodicalIF":12.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529640","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

NIR-II AIEgen nanocomplex with suppressed nonradiative decay and intersystem crossing for high-contrast mesenteric vascular imaging

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-28 DOI: 10.1016/j.biomaterials.2025.123229

Jianlin Liu , Wenjing Liu , Guanghui Liu , Rongfeng Wang , Jing Liu , Xiaogang Zhang , Heping Shi , Xiuqing Dong , Jing Zhao , Dan Ding , Guorui Jin

The prompt assessment of the mesenteric vasculature is crucial for the diagnosis of lethal mesenteric ischemia, underscoring the need for real-time mesenteric vascular imaging using small organic molecules that radiate fluorescence within the second near-infrared spectrum (NIR-II) due to its deep penetration and elevated signal-to-background ratio (SBR), which have been rarely reported. Unfortunately, numerous NIR-II dyes exhibit low quantum yields (QYs) when employed in practical applications, highlighting the need for QY enhancement. For this research, a NIR-II fluorescent AIEgen, termed TPETPA-TQT, was rationally designed by incorporating tetraphenylethylene (TPE)-fused triphenylamine (TPA) into the robust, high QY core of 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT). We further encapsulated this dye within F127 to form the TPETPA-TQT F127 nanocomplex, which exhibits a 6.5-fold enhancement in fluorescence intensity over the TPA-TQT dye encapsulated with DSPE-PEG₂₀₀₀, attributed to the suppression of molecular nonradiative decay and intersystem crossing. The abdominal vasculature and microvessels on the intestinal wall surface, as narrow as 0.41 mm, can real-time visualization using TPETPA-TQT F127 nanocomplex, and exhibit a 94 % improvement of SBR versus ICG. Our findings will push forward the progress of high-brightness NIR-II contrast agents for enhanced mesenteric vasculature imaging and mesenteric ischemia diagnosis.

{"title":"NIR-II AIEgen nanocomplex with suppressed nonradiative decay and intersystem crossing for high-contrast mesenteric vascular imaging","authors":"Jianlin Liu , Wenjing Liu , Guanghui Liu , Rongfeng Wang , Jing Liu , Xiaogang Zhang , Heping Shi , Xiuqing Dong , Jing Zhao , Dan Ding , Guorui Jin","doi":"10.1016/j.biomaterials.2025.123229","DOIUrl":"10.1016/j.biomaterials.2025.123229","url":null,"abstract":"<div><div>The prompt assessment of the mesenteric vasculature is crucial for the diagnosis of lethal mesenteric ischemia, underscoring the need for real-time mesenteric vascular imaging using small organic molecules that radiate fluorescence within the second near-infrared spectrum (NIR-II) due to its deep penetration and elevated signal-to-background ratio (SBR), which have been rarely reported. Unfortunately, numerous NIR-II dyes exhibit low quantum yields (QYs) when employed in practical applications, highlighting the need for QY enhancement. For this research, a NIR-II fluorescent AIEgen, termed TPETPA-TQT, was rationally designed by incorporating tetraphenylethylene (TPE)-fused triphenylamine (TPA) into the robust, high QY core of 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT). We further encapsulated this dye within F127 to form the TPETPA-TQT F127 nanocomplex, which exhibits a 6.5-fold enhancement in fluorescence intensity over the TPA-TQT dye encapsulated with DSPE-PEG<sub>2000</sub>, attributed to the suppression of molecular nonradiative decay and intersystem crossing. The abdominal vasculature and microvessels on the intestinal wall surface, as narrow as 0.41 mm, can real-time visualization using TPETPA-TQT F127 nanocomplex, and exhibit a 94 % improvement of SBR versus ICG. Our findings will push forward the progress of high-brightness NIR-II contrast agents for enhanced mesenteric vasculature imaging and mesenteric ischemia diagnosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123229"},"PeriodicalIF":12.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535137","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

Distinct impacts of aging on the immune responses to extracellular matrix-based versus synthetic biomaterials

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-27 DOI: 10.1016/j.biomaterials.2025.123204

Mangesh M. Kulkarni , Branimir Popovic , Alexis L. Nolfi , Clint D. Skillen , Bryan N. Brown

All implanted materials inevitably trigger an acute inflammatory response. The long-term outcome, however, is dependent on the trajectory of this response. This study investigates the effects of aging on the immune response to two commercially available biomaterials. Extracellular matrix-based urinary bladder matrix (UBM) and synthetic polypropylene mesh (PPM) were implanted in young (4 months) and aged (18 months) C57BL/6J mice. Overall, PPM led to a sustained inflammatory response regardless of the age of the mice. In contrast, UBM induced an initial inflammatory response that matured into a pro-regenerative/remodeling response with time, though aged mice exhibited a delayed resolution of inflammation. The PPM-induced response was predominantly pro-inflammatory with consistently higher M1-like macrophage phenotype, whereas the response to UBM was characterized by an anti-inflammatory M2-like phenotype, especially in young mice. RNA sequencing revealed marked age-related differences in gene transcription. At day 7 post-implantation, the young mice with UBM showed a robust upregulation of both pro- and anti-inflammatory pathways as compared to young mice implanted with PPM, however, by day 14, the gene expression profile transitioned into an anti-inflammatory profile. Intriguingly, in aged mice, the response to UBM was distinct with consistent downregulation of inflammatory genes compared to PPM, while the response to PPM in both young and aged animals was largely consistent. Upstream analysis identified cytokines as key drivers of the host response, with IL-4 and IL-13 in young mice, and TNF-α and IL-1β driving chronic inflammation in aged mice. These findings highlight the importance of host age in biomaterial outcome, and the potential of ECM-based materials to mount a favorable response even in the presence of age-related immune dysregulation.

{"title":"Distinct impacts of aging on the immune responses to extracellular matrix-based versus synthetic biomaterials","authors":"Mangesh M. Kulkarni , Branimir Popovic , Alexis L. Nolfi , Clint D. Skillen , Bryan N. Brown","doi":"10.1016/j.biomaterials.2025.123204","DOIUrl":"10.1016/j.biomaterials.2025.123204","url":null,"abstract":"<div><div>All implanted materials inevitably trigger an acute inflammatory response. The long-term outcome, however, is dependent on the trajectory of this response. This study investigates the effects of aging on the immune response to two commercially available biomaterials. Extracellular matrix-based urinary bladder matrix (UBM) and synthetic polypropylene mesh (PPM) were implanted in young (4 months) and aged (18 months) C57BL/6J mice. Overall, PPM led to a sustained inflammatory response regardless of the age of the mice. In contrast, UBM induced an initial inflammatory response that matured into a pro-regenerative/remodeling response with time, though aged mice exhibited a delayed resolution of inflammation. The PPM-induced response was predominantly pro-inflammatory with consistently higher M1-like macrophage phenotype, whereas the response to UBM was characterized by an anti-inflammatory M2-like phenotype, especially in young mice. RNA sequencing revealed marked age-related differences in gene transcription. At day 7 post-implantation, the young mice with UBM showed a robust upregulation of both pro- and anti-inflammatory pathways as compared to young mice implanted with PPM, however, by day 14, the gene expression profile transitioned into an anti-inflammatory profile. Intriguingly, in aged mice, the response to UBM was distinct with consistent downregulation of inflammatory genes compared to PPM, while the response to PPM in both young and aged animals was largely consistent. Upstream analysis identified cytokines as key drivers of the host response, with IL-4 and IL-13 in young mice, and TNF-α and IL-1β driving chronic inflammation in aged mice. These findings highlight the importance of host age in biomaterial outcome, and the potential of ECM-based materials to mount a favorable response even in the presence of age-related immune dysregulation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123204"},"PeriodicalIF":12.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579549","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}

引用次数: 0

An AIE-active near-infrared molecular probe for migrasome labeling

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-27 DOI: 10.1016/j.biomaterials.2025.123213

Jie Cui , Fei Zhang , Dong Jiang , Boqi Liu , Han Zhang , Niu Niu , Dingyuan Yan , Guangjie Song , Xue Li , Li Yu , Dong Wang , Ben Zhong Tang

Migrasomes, newly identified organelles, play crucial roles in various physiological and pathological activities, including embryogenesis, immune responses, wound healing, and metastasis of cancer cells. Migrasome visualization is essential for the deep exploration of migrasome biology. Despite the reported labeling methods based on migrasome marker proteins, a simple and convenient method for migrasome labeling is more desirable compared to the complicated transfection technique. Here, an aggregation-induced emission (AIE) based near-infrared (NIR) molecular probe named TTCPy was presented, which can bind to the phospholipid on migrasomes and light up migrasomes with a turn-on NIR fluorescence. TTCPy allows for high-performance imaging of migrasomes in both live cells and living chorioallantoic membranes via simple and rapid staining. Moreover, TTCPy achieves live-cell super-resolution imaging of migrasomes, affording remarkedly improved spatial resolution and signal-to-background ratio. This work offers a simple yet powerful tool for migrasome visualization and will contribute to the booming hotspot of migrasome biology.

{"title":"An AIE-active near-infrared molecular probe for migrasome labeling","authors":"Jie Cui , Fei Zhang , Dong Jiang , Boqi Liu , Han Zhang , Niu Niu , Dingyuan Yan , Guangjie Song , Xue Li , Li Yu , Dong Wang , Ben Zhong Tang","doi":"10.1016/j.biomaterials.2025.123213","DOIUrl":"10.1016/j.biomaterials.2025.123213","url":null,"abstract":"<div><div>Migrasomes, newly identified organelles, play crucial roles in various physiological and pathological activities, including embryogenesis, immune responses, wound healing, and metastasis of cancer cells. Migrasome visualization is essential for the deep exploration of migrasome biology. Despite the reported labeling methods based on migrasome marker proteins, a simple and convenient method for migrasome labeling is more desirable compared to the complicated transfection technique. Here, an aggregation-induced emission (AIE) based near-infrared (NIR) molecular probe named TTCPy was presented, which can bind to the phospholipid on migrasomes and light up migrasomes with a turn-on NIR fluorescence. TTCPy allows for high-performance imaging of migrasomes in both live cells and living chorioallantoic membranes via simple and rapid staining. Moreover, TTCPy achieves live-cell super-resolution imaging of migrasomes, affording remarkedly improved spatial resolution and signal-to-background ratio. This work offers a simple yet powerful tool for migrasome visualization and will contribute to the booming hotspot of migrasome biology.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123213"},"PeriodicalIF":12.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529643","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

Corrigendum to ‘A sandwiched microarray platform for benchtop cell-based high throughput screening’ [Biomaterials Volume 32 Issue 3 (2011) 12500]

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-27 DOI: 10.1016/j.biomaterials.2025.123173

Jinhui Wu , Ian Wheeldon , Yuqi Guo , Tingli Lu , Yanan Du , Ben Wang , Jiankang He , Yiqiao Hu , Ali Khademhosseini

引用次数: 0

Engineering long-lived charge separation states boosts type-I ROS generation for efficient cancer therapy 设计长寿命电荷分离态，促进 I 型 ROS 生成，实现高效癌症治疗

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-27 DOI: 10.1016/j.biomaterials.2025.123218

Zhongyan Hu , Wenjing Liu , Jianyu Zhang , Xiaoyu Guo , Huaquan Fang , Junjun Ni , Jacky W.Y. Lam , Ryan T.K. Kwok , Feng Xu , Guorui Jin , Ben Zhong Tang

Organic photosensitizers (PSs) with long-lived charge-separated states (CSs) are optimal for converting photonic energy into reactive oxygen species (ROS) by maximizing the interaction between excited electrons and holes in subsequent photoreactions. However, the substantial consumption of oxygen by the singlet oxygen species produced by these PSs can significantly impede their anticancer efficacy, because of the hypoxia nature of solid tumors. Herein, we present a rational strategy for the structural modification of the well-known Fukuzumi acridinium salt (9-mesityl-10-methylacridinium ion) with long-lived CSs, by incorporating a methyl-substituted diphenylamine group (named MTPAA). This modification significantly enhances type-I ROS generation. The “methyl effect” in MTPAA has distinguished merits of stabilized radical species through resonance, leading to an over 8-fold increase in type-I ROS generation compared to TPAA, which lacks the methyl group. Moreover, cellular experiments show that MTPAA with the “methyl effect” significantly enhances photodynamic therapy efficacy under hypoxic conditions. Our molecular design strategy offers a promising approach to creating high-performance type-I PSs and is anticipated to inspire broader exploration in other photosensitizer systems with long-lived CSs, serving as a versatile strategy for advancing type-I PS development.

具有长寿命电荷分离态（CSs）的有机光敏剂（PSs）能在随后的光反应中最大限度地发挥激发电子和空穴之间的相互作用，是将光子能量转化为活性氧（ROS）的最佳光敏剂。然而，由于实体瘤的缺氧特性，这些 PSs 产生的单线态氧对氧气的大量消耗会严重影响它们的抗癌功效。在此，我们提出了一种合理的策略，通过加入甲基取代的二苯胺基团（命名为 MTPAA），对著名的 Fukuzumi 吖啶鎓盐（9-甲巯基-10-甲基吖啶鎓离子）与长寿命 CSs 进行结构修饰。这种修饰大大增强了 I 型 ROS 的生成。MTPAA 中的 "甲基效应 "具有通过共振稳定自由基物种的突出优点，与缺少甲基的 TPAA 相比，其产生的 I 型 ROS 增加了 8 倍以上。此外，细胞实验表明，在缺氧条件下，具有 "甲基效应 "的 MTPAA 能显著提高光动力疗法的疗效。我们的分子设计策略为创造高性能的 I 型 PS 提供了一种前景广阔的方法，预计将在其他具有长寿命 CS 的光敏剂系统中激发更广泛的探索，成为推动 I 型 PS 开发的一种多功能策略。

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引用次数: 0

Immunity/metabolism dual-regulation via an acidity-triggered bioorthogonal assembly nanoplatform enhances glioblastoma immunotherapy by targeting CXCL12/CXCR4 and adenosine-A2AR pathways

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-26 DOI: 10.1016/j.biomaterials.2025.123216

Ruili Wei , Kunfeng Xie , Tao Li , Wanxian Lin , Yandong Zhao , Jiamin Li , Shengsheng Lai , Xinhua Wei , Xinqing Jiang , Youyong Yuan , Ruimeng Yang

Blocking the C-X-C motif chemokine ligand-12/C-X-C motif chemokine receptor-4 (CXCL12/CXCR4) signal offers the potential to induce immunogenic cell death (ICD) and enhance immunotherapy of glioblastoma (GBM). However, traditional intracellular targeted delivery strategies and adenosine-mediated tumor immunosuppression limit its therapeutic efficacy. Herein, we present an acidity-triggered self-assembly nanoplatform based on bioorthogonal reaction to potentiate GBM immunotherapy through dual regulation of metabolism and immune pathways. AMD3100 (CXCR4 antagonist) and CPI-444 (adenosine 2A receptor inhibitor) were formulated into micelles, denoted as AMD@iNP_DBCO and CPI@iNP_N3, respectively. Upon administration, the pH-sensitive poly(2-azepane ethyl methacrylate) group of AMD@iNP_DBCO responds to the acidic tumor microenvironment, exposing the DBCO moiety, resulting in highly efficient bioorthogonal reaction with azide group on CPI@iNP_N3 to form large-sized aggregates, ensuring extracellular drug release. The combination of AMD3100 and CPI-444 contributes to ICD induction, dendritic cell maturation, and immunosuppressive milieu alleviation by reducing tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, leading to a robust antitumor response, thereby significantly prolonging survival in orthotopic GBM-bearing mice. Furthermore, the nanoplatform remarkably amplifies immuno-radiotherapy by potently evoking cytotoxic CD8⁺ T cell priming, and synergized with immune checkpoint blockade by delaying CD8⁺ T cell exhaustion. Our work highlights the potential of the in situ assembly nanoplatform tailored for delivery of extracellular-targeted therapeutic agents for boosting GBM immunotherapy.

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引用次数: 0

Exosome-capturing scaffold promotes endogenous bone regeneration through neutrophil-derived exosomes by enhancing fast vascularization

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-02-25 DOI: 10.1016/j.biomaterials.2025.123215

Le Wang , Luying Yang , Lei Tian , Baolin Guo , Taiqiang Dai , Qianxin Lv , Jirong Xie , Fuwei Liu , Han Bao , Feng Cao , Ya Liu , Ye Gao , Yan Hou , Zhou Ye , Shenqiang Wang , Qiuyu Zhang , Liang Kong , Bolei Cai

Exosomes (Exos), extracellular vesicles of endosomal origin, are a promising therapeutic platform for tissue regeneration. In the current study, an exosome-capturing scaffold (ECS) was designed to attract and anchor exosomes via electrostatic adherence followed by lipophilic interactions. Our findings demonstrate that local enrichment of exosomes in the ECS implanted into critical mandibular defects could significantly accelerate endogenous bone regeneration by enhancing vascularization at the defect site. Notably, neutrophil (PMN)-derived exosomes (PMN-Exos) were identified as the predominant exosome subtype among all captured exosomes. During endogenous bone regeneration, PMN-Exos promoted endogenous vascularization primarily by stimulating the proliferation of endothelial progenitor cells (EPCs), which play a pivotal role in the vasculogenesis of new blood vessels. Mechanistically, vascularization involved PMN-Exo-derived miR455-3p, which promotes EPC proliferation by targeting the Smad4 pathway. In conclusion, this study offers an ECS with broad application prospects for enhancing tissue regeneration by accelerating vascularization. The elucidation of underlying mechanisms paves the way for developing novel strategies to regenerate various tissues and organs.

{"title":"Exosome-capturing scaffold promotes endogenous bone regeneration through neutrophil-derived exosomes by enhancing fast vascularization","authors":"Le Wang , Luying Yang , Lei Tian , Baolin Guo , Taiqiang Dai , Qianxin Lv , Jirong Xie , Fuwei Liu , Han Bao , Feng Cao , Ya Liu , Ye Gao , Yan Hou , Zhou Ye , Shenqiang Wang , Qiuyu Zhang , Liang Kong , Bolei Cai","doi":"10.1016/j.biomaterials.2025.123215","DOIUrl":"10.1016/j.biomaterials.2025.123215","url":null,"abstract":"<div><div>Exosomes (Exos), extracellular vesicles of endosomal origin, are a promising therapeutic platform for tissue regeneration. In the current study, an exosome-capturing scaffold (ECS) was designed to attract and anchor exosomes via electrostatic adherence followed by lipophilic interactions. Our findings demonstrate that local enrichment of exosomes in the ECS implanted into critical mandibular defects could significantly accelerate endogenous bone regeneration by enhancing vascularization at the defect site. Notably, neutrophil (PMN)-derived exosomes (PMN-Exos) were identified as the predominant exosome subtype among all captured exosomes. During endogenous bone regeneration, PMN-Exos promoted endogenous vascularization primarily by stimulating the proliferation of endothelial progenitor cells (EPCs), which play a pivotal role in the vasculogenesis of new blood vessels. Mechanistically, vascularization involved PMN-Exo-derived miR455-3p, which promotes EPC proliferation by targeting the Smad4 pathway. In conclusion, this study offers an ECS with broad application prospects for enhancing tissue regeneration by accelerating vascularization. The elucidation of underlying mechanisms paves the way for developing novel strategies to regenerate various tissues and organs.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123215"},"PeriodicalIF":12.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519330","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