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Intranasal delivery of AEP inhibitor-loaded neuron-targeted liposome ameliorates radiation-induced brain injury
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-11 DOI: 10.1016/j.mtbio.2025.101568
Keman Liao , Yan Gao , Mengdan Cheng , Yibing Zhang , Jianyi Zhao , Li Zhou , Ran Wu , Gang Cai , Lu Cao , Jiayi Chen , Yingying Lin
Acute exposure to high-dose radiation during head and neck tumors radiotherapy can result in radiation-induced brain injury (RIBI), characterized by neurocognitive deficits, dementia, and epilepsy. Asparagine endopeptidase (AEP), a cysteine proteinase, is effective in preventing neurodegenerative diseases and RIBI. However, the limited permeability of selective AEP inhibitor (AEPI) delivery to the brain reduces its effectiveness in preventing RIBI. This study constructed a nose-to-brain delivery platform for AEPI by encapsulating it in liposomes that are surface modified with rabies virus glycoprotein (RVG29), creating RVG29-AEPI liposomes. These RVG29-AEPI liposomes demonstrated efficient cellular uptake and blood-brain barrier penetration in vitro and in vivo. RVG29-AEPI liposomes effectively shielded DNA from radiation-induced damage and resulted in more effective reactive oxygen species removal than liposomes in primary neurons and microglial cells. Notably, the treatment with RVG29-AEPI liposomes (10 mg/kg AEPI) was highly systemically safe and significantly reduced brain injury. Behavioral tests demonstrated that RVG29-AEPI liposomes-treated mice had less radiation-induced brain damage and motor dysfunction. Moreover, it significantly prevented neuronal injury and microglia cell activation under photon and modern proton irradiation. These findings demonstrate the potential of nose-to-brain medication delivery of RVG29-AEPI liposomes for effective radioprotection, indicating a viable technique with enormous potential for clinical translation.
{"title":"Intranasal delivery of AEP inhibitor-loaded neuron-targeted liposome ameliorates radiation-induced brain injury","authors":"Keman Liao ,&nbsp;Yan Gao ,&nbsp;Mengdan Cheng ,&nbsp;Yibing Zhang ,&nbsp;Jianyi Zhao ,&nbsp;Li Zhou ,&nbsp;Ran Wu ,&nbsp;Gang Cai ,&nbsp;Lu Cao ,&nbsp;Jiayi Chen ,&nbsp;Yingying Lin","doi":"10.1016/j.mtbio.2025.101568","DOIUrl":"10.1016/j.mtbio.2025.101568","url":null,"abstract":"<div><div>Acute exposure to high-dose radiation during head and neck tumors radiotherapy can result in radiation-induced brain injury (RIBI), characterized by neurocognitive deficits, dementia, and epilepsy. Asparagine endopeptidase (AEP), a cysteine proteinase, is effective in preventing neurodegenerative diseases and RIBI. However, the limited permeability of selective AEP inhibitor (AEPI) delivery to the brain reduces its effectiveness in preventing RIBI. This study constructed a nose-to-brain delivery platform for AEPI by encapsulating it in liposomes that are surface modified with rabies virus glycoprotein (RVG29), creating RVG29-AEPI liposomes. These RVG29-AEPI liposomes demonstrated efficient cellular uptake and blood-brain barrier penetration <em>in vitro</em> and <em>in vivo</em>. RVG29-AEPI liposomes effectively shielded DNA from radiation-induced damage and resulted in more effective reactive oxygen species removal than liposomes in primary neurons and microglial cells. Notably, the treatment with RVG29-AEPI liposomes (10 mg/kg AEPI) was highly systemically safe and significantly reduced brain injury. Behavioral tests demonstrated that RVG29-AEPI liposomes-treated mice had less radiation-induced brain damage and motor dysfunction. Moreover, it significantly prevented neuronal injury and microglia cell activation under photon and modern proton irradiation. These findings demonstrate the potential of nose-to-brain medication delivery of RVG29-AEPI liposomes for effective radioprotection, indicating a viable technique with enormous potential for clinical translation.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101568"},"PeriodicalIF":8.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419689","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
Dual-Action flavonol carbonized polymer dots spray: Accelerating burn wound recovery through immune responses modulation and EMT induction
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-11 DOI: 10.1016/j.mtbio.2025.101572
Liuyi Du , Xu Zhang , Lei Huang , Mingxi Yang , Wenbin Zhang , Jiaqi Xu , Junguang Liu , Wangni Xie , Xue Zhang , Kexuan Liu , Wenhao Zhai , Linlin Wen , Boya Zhang , Rongrong Ye , Lijun Liu , Huan Wang , Hongchen Sun , Daowei Li
Effective immune homeostasis modulation and re-epithelialization promotion are crucial for accelerating burn wound healing. Cell migration is fundamental to re-epithelialization, with epithelial-mesenchymal transition (EMT) as a key mechanism. A sustained inflammatory environment or impaired macrophage transition to M2 phenotype can hinder pro-resolving cytokine activation, further delaying the recruitment, migration, and re-epithelialization of epidermal cells to the injury site, ultimately compromising wound healing. Herein, the bioactive flavonol quercetin is transformed into pharmacologically active carbonized polymer dots (Qu-CDs) spray with high water dispersibility, permeability and biocompatibility for full-thickness skin burns treatment. Qu-CDs spray can efficiently initiate macrophage reprogramming and promote the transition of macrophages from M1 to M2 phenotype, modulating immune responses and facilitating the shift from the inflammatory phase to re-epithelialization. Additionally, Qu-CDs spray can promote cell migration and re-epithelialization of wound edge epithelial cells by inducing an EMT process without growth factors, further accelerating the reconstruction of the normal epidermal barrier. Mechanistically, Qu-CDs spray activates the smad1/5 signaling pathway for promoting the EMT phenotype of wound edge epithelial cells. Overall, this study facilitates the construction of novel spray dosage form of pharmacologically active carbonized polymer dots with desired bioactivities for effective wound healing.
{"title":"Dual-Action flavonol carbonized polymer dots spray: Accelerating burn wound recovery through immune responses modulation and EMT induction","authors":"Liuyi Du ,&nbsp;Xu Zhang ,&nbsp;Lei Huang ,&nbsp;Mingxi Yang ,&nbsp;Wenbin Zhang ,&nbsp;Jiaqi Xu ,&nbsp;Junguang Liu ,&nbsp;Wangni Xie ,&nbsp;Xue Zhang ,&nbsp;Kexuan Liu ,&nbsp;Wenhao Zhai ,&nbsp;Linlin Wen ,&nbsp;Boya Zhang ,&nbsp;Rongrong Ye ,&nbsp;Lijun Liu ,&nbsp;Huan Wang ,&nbsp;Hongchen Sun ,&nbsp;Daowei Li","doi":"10.1016/j.mtbio.2025.101572","DOIUrl":"10.1016/j.mtbio.2025.101572","url":null,"abstract":"<div><div>Effective immune homeostasis modulation and re-epithelialization promotion are crucial for accelerating burn wound healing. Cell migration is fundamental to re-epithelialization, with epithelial-mesenchymal transition (EMT) as a key mechanism. A sustained inflammatory environment or impaired macrophage transition to M2 phenotype can hinder pro-resolving cytokine activation, further delaying the recruitment, migration, and re-epithelialization of epidermal cells to the injury site, ultimately compromising wound healing. Herein, the bioactive flavonol quercetin is transformed into pharmacologically active carbonized polymer dots (Qu-CDs) spray with high water dispersibility, permeability and biocompatibility for full-thickness skin burns treatment. Qu-CDs spray can efficiently initiate macrophage reprogramming and promote the transition of macrophages from M1 to M2 phenotype, modulating immune responses and facilitating the shift from the inflammatory phase to re-epithelialization. Additionally, Qu-CDs spray can promote cell migration and re-epithelialization of wound edge epithelial cells by inducing an EMT process without growth factors, further accelerating the reconstruction of the normal epidermal barrier. Mechanistically, Qu-CDs spray activates the smad1/5 signaling pathway for promoting the EMT phenotype of wound edge epithelial cells. Overall, this study facilitates the construction of novel spray dosage form of pharmacologically active carbonized polymer dots with desired bioactivities for effective wound healing.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101572"},"PeriodicalIF":8.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419687","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
Tissue-specific extracellular matrix for the larger-scaled expansion of spinal cord organoids
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-11 DOI: 10.1016/j.mtbio.2025.101561
Yanjun Guan , Zhibo Jia , Xing Xiong , Ruichao He , Yiben Ouyang , Haolin Liu , Lijing Liang , Xiaoran Meng , Ranran Zhang , Congcong Guan , Sice Wang , Dongdong Li , Yuhui Cui , Jun Bai , Jinjuan Zhao , Haoye Meng , Jiang Peng , Yu Wang
Spinal cord organoids (SCOs) are in vitro models that faithfully recapitulate the basic tissue architecture and cell types of the spinal cord and play a crucial role in developmental studies, disease modeling, and drug screening. Physiological cues are required for proliferation and differentiation during SCO culture. However, commonly used basement membrane matrix products, such as Matrigel®, lack tissue-specific biophysical signals. The current study utilizes decellularization process to fabricate tissue-derived hydrogel from porcine spinal cord tissue that retain intrinsic matrix components. This gel system supported an expanded neuroepithelial scale and enhanced ventral recognition patterns during SCO cultivation. Based on the characteristics of the enlarged aggregate size, a technical system for SCO cutting and subculture are proposed to improve the economic feasibility. Finally, the advantage of S-gel in maintaining neurite outgrowth are also found, which suggests its potential application in neural-related microphysiological systems.
{"title":"Tissue-specific extracellular matrix for the larger-scaled expansion of spinal cord organoids","authors":"Yanjun Guan ,&nbsp;Zhibo Jia ,&nbsp;Xing Xiong ,&nbsp;Ruichao He ,&nbsp;Yiben Ouyang ,&nbsp;Haolin Liu ,&nbsp;Lijing Liang ,&nbsp;Xiaoran Meng ,&nbsp;Ranran Zhang ,&nbsp;Congcong Guan ,&nbsp;Sice Wang ,&nbsp;Dongdong Li ,&nbsp;Yuhui Cui ,&nbsp;Jun Bai ,&nbsp;Jinjuan Zhao ,&nbsp;Haoye Meng ,&nbsp;Jiang Peng ,&nbsp;Yu Wang","doi":"10.1016/j.mtbio.2025.101561","DOIUrl":"10.1016/j.mtbio.2025.101561","url":null,"abstract":"<div><div>Spinal cord organoids (SCOs) are in vitro models that faithfully recapitulate the basic tissue architecture and cell types of the spinal cord and play a crucial role in developmental studies, disease modeling, and drug screening. Physiological cues are required for proliferation and differentiation during SCO culture. However, commonly used basement membrane matrix products, such as Matrigel®, lack tissue-specific biophysical signals. The current study utilizes decellularization process to fabricate tissue-derived hydrogel from porcine spinal cord tissue that retain intrinsic matrix components. This gel system supported an expanded neuroepithelial scale and enhanced ventral recognition patterns during SCO cultivation. Based on the characteristics of the enlarged aggregate size, a technical system for SCO cutting and subculture are proposed to improve the economic feasibility. Finally, the advantage of S-gel in maintaining neurite outgrowth are also found, which suggests its potential application in neural-related microphysiological systems.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101561"},"PeriodicalIF":8.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453336","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
Biomimetic mineralized DCPA/ anti-CD47 containing thermo-sensitive injectable hydrogel for bone-metastatic prostate cancer treatment
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-11 DOI: 10.1016/j.mtbio.2025.101573
Shenglong Tan , Qianqian Wang , Chunxiang Feng , Xiaoyong Pu , Dong Li , Fenglian Jiang , Jian Wu , Shang Huang , Junhong Fan , Ruijuan Zhong , Chunmiao Mo , Jiayu Luo , Peiliang Zhong , Jiumin Liu , Dandan Ma
Strategies that leverage the phagocytic capabilities of M1 macrophages against tumor cells are currently being investigated for cancer treatment. However, the clinical application of these strategies is significantly hampered by the severe side effects associated with conventional M1 macrophage activators. In this study, biomimetic mineralized dicalcium phosphate anhydrous (MDCPA) was synthesized using Zein as an organic template, aiming to promote M1 macrophage polarization effectively while minimizing side effects. In vitro experiments demonstrated that MDCPA can be engulfed by macrophages and induce M1 macrophage polarization. By combining the stimulation of MDCPA with a commonly used immune checkpoint inhibitor, anti-CD47 (aCD47), the macrophages exhibited the highest phagocytic activity toward prostate cancer cells. Further in vivo experiments illustrated significant tumor suppression and reduced bone resorption in a prostate cancer bone metastasis model utilizing MDCPA/aCD47-containing thermos-sensitive injectable hydrogels (MDCPA/aCD47 TSI gel). Mechanistic studies indicated that the MDCPA/aCD47 TSI gel promotes tumor cell apoptosis not only through the phagocytosis of tumor cells mediated by M1 macrophages, but also by activating anti-tumor CD8-positive T cells. Consequently, this composite gel platform presents an effective theragnostic strategy for treating prostate cancer bone metastasis without the associated side effects, facilitated by biomimetic minerals that mediate anti-tumor immunity.
{"title":"Biomimetic mineralized DCPA/ anti-CD47 containing thermo-sensitive injectable hydrogel for bone-metastatic prostate cancer treatment","authors":"Shenglong Tan ,&nbsp;Qianqian Wang ,&nbsp;Chunxiang Feng ,&nbsp;Xiaoyong Pu ,&nbsp;Dong Li ,&nbsp;Fenglian Jiang ,&nbsp;Jian Wu ,&nbsp;Shang Huang ,&nbsp;Junhong Fan ,&nbsp;Ruijuan Zhong ,&nbsp;Chunmiao Mo ,&nbsp;Jiayu Luo ,&nbsp;Peiliang Zhong ,&nbsp;Jiumin Liu ,&nbsp;Dandan Ma","doi":"10.1016/j.mtbio.2025.101573","DOIUrl":"10.1016/j.mtbio.2025.101573","url":null,"abstract":"<div><div>Strategies that leverage the phagocytic capabilities of M1 macrophages against tumor cells are currently being investigated for cancer treatment. However, the clinical application of these strategies is significantly hampered by the severe side effects associated with conventional M1 macrophage activators. In this study, biomimetic mineralized dicalcium phosphate anhydrous (MDCPA) was synthesized using Zein as an organic template, aiming to promote M1 macrophage polarization effectively while minimizing side effects. <em>In vitro</em> experiments demonstrated that MDCPA can be engulfed by macrophages and induce M1 macrophage polarization. By combining the stimulation of MDCPA with a commonly used immune checkpoint inhibitor, anti-CD47 (aCD47), the macrophages exhibited the highest phagocytic activity toward prostate cancer cells. Further <em>in vivo</em> experiments illustrated significant tumor suppression and reduced bone resorption in a prostate cancer bone metastasis model utilizing MDCPA/aCD47-containing thermos-sensitive injectable hydrogels (MDCPA/aCD47 TSI gel). Mechanistic studies indicated that the MDCPA/aCD47 TSI gel promotes tumor cell apoptosis not only through the phagocytosis of tumor cells mediated by M1 macrophages, but also by activating anti-tumor CD8-positive T cells. Consequently, this composite gel platform presents an effective theragnostic strategy for treating prostate cancer bone metastasis without the associated side effects, facilitated by biomimetic minerals that mediate anti-tumor immunity.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101573"},"PeriodicalIF":8.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436407","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 MXene nanocomposite hydrogel for enhanced diabetic infected wound healing via photothermal antibacterial properties and bioactive molecule integration
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-08 DOI: 10.1016/j.mtbio.2025.101538
Xue Ou , Zhijie Yu , Xi Zheng, Le Chen, Chuanyu Pan, Dandan Li, Zhenzhen Qiao, Xiaoyuan Zheng
Diabetic wounds are a major clinical challenge due to their chronic, non-healing nature, which significantly impacts patients' quality of life. Traditional treatments often fail to effectively promote wound healing, highlighting the need for new biomaterials. In this study, we developed a composite hydrogel (KC@PF@TA) that combines the photothermal and antibacterial properties of Ti₃C₂Tx-Ag (Titanium carbide-silver) with the regenerative effects of paeoniflorin (PF). The hydrogel was optimized by adjusting the composition, crosslinking density, and the incorporation of nanoparticles, which enhanced its mechanical strength, photothermal conversion efficiency, antibacterial properties, and biocompatibility. The optimized hydrogel demonstrated enhanced cell proliferation, migration, and robust photothermal and antibacterial properties in vitro. In a diabetic murine model of Staphylococcus aureus-infected wounds, KC@PF@TA exhibited exceptional therapeutic benefits in antibacterial, anti-inflammatory, angiogenic, and tissue regeneration. Overall, our results suggest that composite hydrogels with controlled bioactive agent release and mechanical modulation present a promising solution for treating chronic diabetic wounds.
{"title":"An MXene nanocomposite hydrogel for enhanced diabetic infected wound healing via photothermal antibacterial properties and bioactive molecule integration","authors":"Xue Ou ,&nbsp;Zhijie Yu ,&nbsp;Xi Zheng,&nbsp;Le Chen,&nbsp;Chuanyu Pan,&nbsp;Dandan Li,&nbsp;Zhenzhen Qiao,&nbsp;Xiaoyuan Zheng","doi":"10.1016/j.mtbio.2025.101538","DOIUrl":"10.1016/j.mtbio.2025.101538","url":null,"abstract":"<div><div>Diabetic wounds are a major clinical challenge due to their chronic, non-healing nature, which significantly impacts patients' quality of life. Traditional treatments often fail to effectively promote wound healing, highlighting the need for new biomaterials. In this study, we developed a composite hydrogel (KC@PF@TA) that combines the photothermal and antibacterial properties of Ti₃C₂Tx-Ag (Titanium carbide-silver) with the regenerative effects of paeoniflorin (PF). The hydrogel was optimized by adjusting the composition, crosslinking density, and the incorporation of nanoparticles, which enhanced its mechanical strength, photothermal conversion efficiency, antibacterial properties, and biocompatibility. The optimized hydrogel demonstrated enhanced cell proliferation, migration, and robust photothermal and antibacterial properties in vitro. In a diabetic murine model of <em>Staphylococcus aureus</em>-infected wounds, KC@PF@TA exhibited exceptional therapeutic benefits in antibacterial, anti-inflammatory, angiogenic, and tissue regeneration. Overall, our results suggest that composite hydrogels with controlled bioactive agent release and mechanical modulation present a promising solution for treating chronic diabetic wounds.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101538"},"PeriodicalIF":8.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395665","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 aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-08 DOI: 10.1016/j.mtbio.2025.101564
Hang Zou , Pingping Wang , Zhihao Bai , Liping Liu , Jingtong Wang , Yanfang Cheng , Bairong He , Zujin Zhao , Lei Zheng
Therapeutic resistance is a major challenge in clinical cancer theranostics, often leading to treatment failure and increased patient mortality. Breaking this therapeutic deadlock, enhancing the efficacy of clinical treatments, and ultimately improving patient survival rates are both highly desirable and significantly challenging goals. Herein, we have developed a new fluorescent luminogen, QM-DMAC, which features aggregation-induced emission (AIE), and exceptional viscosity-responsive properties. The AIE-active QM-DMAC can specifically stain lysosomes in tumor cells, offering a high signal-to-noise ratio and enabling specific visualization of variations in lysosomal viscosity, such as those induced by inflammation or autophagy. Furthermore, QM-DMAC effectively generates reactive oxygen species (ROS) under white light irradiation, which precisely induces ROS-mediated lysosomal membrane permeabilization (LMP) and lysosome rupture. This ultimately causes severe cell damage and restores the sensitivity of tumor cells to radiotherapy and chemotherapy. Thus, QM-DMAC serves as a highly efficient lysosome-targeting photosensitizer and an excellent therapeutic sensitizer. This innovative “lysosome hijacking” strategy significantly maximizes the efficacy of photodynamic therapy, conquering therapeutic resistance and boosting the synergistic therapeutic effect when integrated with conventional radiotherapy or chemotherapy. It provides a novel approach to the design of theranostic agents for clinical cancer theranostics.
{"title":"An aggregation-induced emission-active lysosome hijacker: Sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance","authors":"Hang Zou ,&nbsp;Pingping Wang ,&nbsp;Zhihao Bai ,&nbsp;Liping Liu ,&nbsp;Jingtong Wang ,&nbsp;Yanfang Cheng ,&nbsp;Bairong He ,&nbsp;Zujin Zhao ,&nbsp;Lei Zheng","doi":"10.1016/j.mtbio.2025.101564","DOIUrl":"10.1016/j.mtbio.2025.101564","url":null,"abstract":"<div><div>Therapeutic resistance is a major challenge in clinical cancer theranostics, often leading to treatment failure and increased patient mortality. Breaking this therapeutic deadlock, enhancing the efficacy of clinical treatments, and ultimately improving patient survival rates are both highly desirable and significantly challenging goals. Herein, we have developed a new fluorescent luminogen, QM-DMAC, which features aggregation-induced emission (AIE), and exceptional viscosity-responsive properties. The AIE-active QM-DMAC can specifically stain lysosomes in tumor cells, offering a high signal-to-noise ratio and enabling specific visualization of variations in lysosomal viscosity, such as those induced by inflammation or autophagy. Furthermore, QM-DMAC effectively generates reactive oxygen species (ROS) under white light irradiation, which precisely induces ROS-mediated lysosomal membrane permeabilization (LMP) and lysosome rupture. This ultimately causes severe cell damage and restores the sensitivity of tumor cells to radiotherapy and chemotherapy. Thus, QM-DMAC serves as a highly efficient lysosome-targeting photosensitizer and an excellent therapeutic sensitizer. This innovative “lysosome hijacking” strategy significantly maximizes the efficacy of photodynamic therapy, conquering therapeutic resistance and boosting the synergistic therapeutic effect when integrated with conventional radiotherapy or chemotherapy. It provides a novel approach to the design of theranostic agents for clinical cancer theranostics.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101564"},"PeriodicalIF":8.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379416","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
Inhaled predatory bacteria-loaded large porous microspheres to eradicate drug-resistant Pseudomonas aeruginosa from the lung
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-08 DOI: 10.1016/j.mtbio.2025.101562
Yan Liu , Wanmei Wang , Ruiteng Li , Hui Zhang , Wanting Guo , Bochuan Yuan , Lina Du , Yiguang Jin
The pneumonia caused by antimicrobial-resistant Gram-negative bacteria is an intractable clinical problem due to the lack of effective treatments. Inspired by the unique predatory bacterial ability of Bdellovibrio bacteriovorus, we here developed an inhalable live bacterial formulations, i.e., B. bacteriovorus-loaded poly(lactic-co-glycolic acid) (PLGA) large porous microspheres (BPMs), to eradicate antimicrobial-resistant Pseudomonas aeruginosa from the lung. BPMs serve as a "safe house" of B. bacteriovorus to avoid being phagocytized by macrophages due to their large size; while the continual release of B. bacteriovorus at the infection site is achieved. We proved BPMs had good biosafety, pulmonary inhalation properties, and antimicrobial effects. The infected mice showed reduced inflammation and lung injury and their respiratory function was well recovered. BPMs have great potential as dry powder inhalers for the treatment of bacterial pneumonia. Inhaled BPMs are an effective treatment against drug-resistant bacterial pneumonia and this live medication is expected to be an alternative therapy to antibiotics.
{"title":"Inhaled predatory bacteria-loaded large porous microspheres to eradicate drug-resistant Pseudomonas aeruginosa from the lung","authors":"Yan Liu ,&nbsp;Wanmei Wang ,&nbsp;Ruiteng Li ,&nbsp;Hui Zhang ,&nbsp;Wanting Guo ,&nbsp;Bochuan Yuan ,&nbsp;Lina Du ,&nbsp;Yiguang Jin","doi":"10.1016/j.mtbio.2025.101562","DOIUrl":"10.1016/j.mtbio.2025.101562","url":null,"abstract":"<div><div>The pneumonia caused by antimicrobial-resistant Gram-negative bacteria is an intractable clinical problem due to the lack of effective treatments. Inspired by the unique predatory bacterial ability of <em>Bdellovibrio bacteriovorus</em>, we here developed an inhalable live bacterial formulations, i.e., <em>B. bacteriovorus</em>-loaded poly(lactic-co-glycolic acid) (PLGA) large porous microspheres (BPMs), to eradicate antimicrobial-resistant <em>Pseudomonas aeruginosa</em> from the lung. BPMs serve as a \"safe house\" of <em>B. bacteriovorus</em> to avoid being phagocytized by macrophages due to their large size; while the continual release of <em>B. bacteriovorus</em> at the infection site is achieved. We proved BPMs had good biosafety, pulmonary inhalation properties, and antimicrobial effects. The infected mice showed reduced inflammation and lung injury and their respiratory function was well recovered. BPMs have great potential as dry powder inhalers for the treatment of bacterial pneumonia. Inhaled BPMs are an effective treatment against drug-resistant bacterial pneumonia and this live medication is expected to be an alternative therapy to antibiotics.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101562"},"PeriodicalIF":8.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387401","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
Recent progress of artificial cells in structure design, functionality and the prospects in food biotechnology
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-08 DOI: 10.1016/j.mtbio.2025.101565
Li Li , Xiaolin Yao , Guoliang Li , Qianqian Guo , Juan Yue , Wenguang Liu , Yapeng Fang , Adam Midgley , Mouming Zhao , Katsuyoshi Nishinari
Artificial cells have bridged the gap between non-living systems and biological cells. In recent years, artificial cells designed to simulate cellular structure and function have garnered significant attention. These artificial cells demonstrate vast potential for advancements in various biomedical areas, including simulating cell structure and function, creating innovative biosensors, facilitating bioactives transport, enabling micro and nanoreactors, and improving the targeted therapy for chronic foodborne diseases. In the interdisciplinary field of artificial cell construction, based on their constituent components, these systems can be categorized into lipid/polymer vesicles, coacervate, colloidosome, and metal-organic framework (MOF) artificial cells. They are anticipated to significantly enhance advancements in food science, particularly in cellular structure optimization, precise nutrition delivery, targeted nutrient release, and rapid detection methods. Consequently, this paper will comprehensively cover the historical background, fabrication techniques, and structural characteristics of artificial cells. From a functional design perspective, this review examines the growth and division mechanisms, energy production processes, encapsulation and reaction vessels, carriers, and information exchange systems of artificial cells. Ultimately, it provides a comprehensive evaluation of the safety of artificial cells from both biological and environmental viewpoints, to introduce and expand the application scenarios of this innovative biotechnology in food science.
{"title":"Recent progress of artificial cells in structure design, functionality and the prospects in food biotechnology","authors":"Li Li ,&nbsp;Xiaolin Yao ,&nbsp;Guoliang Li ,&nbsp;Qianqian Guo ,&nbsp;Juan Yue ,&nbsp;Wenguang Liu ,&nbsp;Yapeng Fang ,&nbsp;Adam Midgley ,&nbsp;Mouming Zhao ,&nbsp;Katsuyoshi Nishinari","doi":"10.1016/j.mtbio.2025.101565","DOIUrl":"10.1016/j.mtbio.2025.101565","url":null,"abstract":"<div><div>Artificial cells have bridged the gap between non-living systems and biological cells. In recent years, artificial cells designed to simulate cellular structure and function have garnered significant attention. These artificial cells demonstrate vast potential for advancements in various biomedical areas, including simulating cell structure and function, creating innovative biosensors, facilitating bioactives transport, enabling micro and nanoreactors, and improving the targeted therapy for chronic foodborne diseases. In the interdisciplinary field of artificial cell construction, based on their constituent components, these systems can be categorized into lipid/polymer vesicles, coacervate, colloidosome, and metal-organic framework (MOF) artificial cells. They are anticipated to significantly enhance advancements in food science, particularly in cellular structure optimization, precise nutrition delivery, targeted nutrient release, and rapid detection methods. Consequently, this paper will comprehensively cover the historical background, fabrication techniques, and structural characteristics of artificial cells. From a functional design perspective, this review examines the growth and division mechanisms, energy production processes, encapsulation and reaction vessels, carriers, and information exchange systems of artificial cells. Ultimately, it provides a comprehensive evaluation of the safety of artificial cells from both biological and environmental viewpoints, to introduce and expand the application scenarios of this innovative biotechnology in food science.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101565"},"PeriodicalIF":8.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378945","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
Dental plaque-inspired peptide engineered to control plaque accumulation
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-08 DOI: 10.1016/j.mtbio.2025.101570
Huixue Wu , Yiran Qin , Kexin Li , Xinning Dai , Minghong Zhou , Zongheng Cen , Yan Li , Zhike Huang , Shuyi Wu
Effective control of plaque accumulation is an important strategy for reducing the risk of both localized oral health issues and systemic diseases associated with plaque. However, existing approaches for preventing plaque accumulation exhibit some limitations, such as insufficient compatibility with the oral microbiota and tissues, as well as inconvenience in their use. Herein, inspired by dental plaque, a new class of peptides featuring excellent anti-fouling performance is successfully developed. Our peptides consist of a salivary-acquired peptide with tooth surface-selective adhesion, a zwitterionic peptide with anti-adhesion property, and four proline residues that provide structural rigidity. We conduct a series of progressive experiments, including molecular dynamics simulation and assessments of the anti-fouling performance of our peptides on hydroxyapatite slices, human tooth enamel slices, and ex vivo human teeth. The results demonstrate that our peptides possess the abilities of rapid anchoring on tooth surfaces and effective inhibiting protein and bacterial adhesion. These characteristics enable our peptide to efficiently control plaque accumulation through rinsing or spraying while preserving the balance of the oral microbiota. These findings open an appealing avenue for the development of anti-fouling agents for controlling plaque accumulation on tooth surfaces.
{"title":"Dental plaque-inspired peptide engineered to control plaque accumulation","authors":"Huixue Wu ,&nbsp;Yiran Qin ,&nbsp;Kexin Li ,&nbsp;Xinning Dai ,&nbsp;Minghong Zhou ,&nbsp;Zongheng Cen ,&nbsp;Yan Li ,&nbsp;Zhike Huang ,&nbsp;Shuyi Wu","doi":"10.1016/j.mtbio.2025.101570","DOIUrl":"10.1016/j.mtbio.2025.101570","url":null,"abstract":"<div><div>Effective control of plaque accumulation is an important strategy for reducing the risk of both localized oral health issues and systemic diseases associated with plaque. However, existing approaches for preventing plaque accumulation exhibit some limitations, such as insufficient compatibility with the oral microbiota and tissues, as well as inconvenience in their use. Herein, inspired by dental plaque, a new class of peptides featuring excellent anti-fouling performance is successfully developed. Our peptides consist of a salivary-acquired peptide with tooth surface-selective adhesion, a zwitterionic peptide with anti-adhesion property, and four proline residues that provide structural rigidity. We conduct a series of progressive experiments, including molecular dynamics simulation and assessments of the anti-fouling performance of our peptides on hydroxyapatite slices, human tooth enamel slices, and ex vivo human teeth. The results demonstrate that our peptides possess the abilities of rapid anchoring on tooth surfaces and effective inhibiting protein and bacterial adhesion. These characteristics enable our peptide to efficiently control plaque accumulation through rinsing or spraying while preserving the balance of the oral microbiota. These findings open an appealing avenue for the development of anti-fouling agents for controlling plaque accumulation on tooth surfaces.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101570"},"PeriodicalIF":8.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465085","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
A tumor-targeting black phosphorus-based nanoplatform for controlled chemo-photothermal therapy of breast cancer
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-07 DOI: 10.1016/j.mtbio.2025.101563
Lin Yang , Ying Zhang , Jing Liu , Xiaofen Wang , Li Zhang , Hao Wan
Combination therapy with high efficacy and precision shows great potential in breast cancer treatment. Herein, we developed a multifunctional nanocarrier (NBP@mSiO2-PEG-cRGD) for tumor-targeting chemo-photothermal therapy of breast cancer in a controlled manner. The nanocarrier was constructed by enveloping nano-sized black phosphorus (NBP) within a mesoporous silica shell (mSiO2) modified with the tumor-targeting peptide c(Arg-Gly-Asp-dPhe-Cys) (cRGD). Due to the existence of pore channels within mSiO2, NBP@mSiO2-PEG-cRGD achieved high loading efficiency of indole-3-carbinol (I3C) molecules (NBP@mSiO2-PEG-cRGD/I3C), an anti-tumor agent derived from food. Mediated by cRGD/integrin αvβ3 interaction, NBP@mSiO2-PEG-cRGD/I3C reached breast tumors in a targeted manner. Once irradiated by the near-infrared laser, our nanocarrier exhibited superior photothermal conversion, which not only induced photothermal therapy but also facilitated the release of I3C from NBP@mSiO2-PEG-cRGD/I3C within tumor cells to inhibit the activation of proto-oncogenic phosphoinositide 3-kinase (PI3K)-AKT signaling pathway and drive chemotherapy. All these attributes contributed to a satisfactory therapeutic effect toward breast tumors, manifesting in significant inhibition of cell proliferation, promotion of cell apoptosis, and reduction of tumor micro-vessel formation, which led to the efficient inhibition of tumor growth. Collectively, the nanocarrier developed here provided useful insights into the development of multifunctional platforms to effectively combat cancer.
{"title":"A tumor-targeting black phosphorus-based nanoplatform for controlled chemo-photothermal therapy of breast cancer","authors":"Lin Yang ,&nbsp;Ying Zhang ,&nbsp;Jing Liu ,&nbsp;Xiaofen Wang ,&nbsp;Li Zhang ,&nbsp;Hao Wan","doi":"10.1016/j.mtbio.2025.101563","DOIUrl":"10.1016/j.mtbio.2025.101563","url":null,"abstract":"<div><div>Combination therapy with high efficacy and precision shows great potential in breast cancer treatment. Herein, we developed a multifunctional nanocarrier (NBP@mSiO<sub>2</sub>-PEG-cRGD) for tumor-targeting chemo-photothermal therapy of breast cancer in a controlled manner. The nanocarrier was constructed by enveloping nano-sized black phosphorus (NBP) within a mesoporous silica shell (mSiO<sub>2</sub>) modified with the tumor-targeting peptide c(Arg-Gly-Asp-dPhe-Cys) (cRGD). Due to the existence of pore channels within mSiO<sub>2</sub>, NBP@mSiO<sub>2</sub>-PEG-cRGD achieved high loading efficiency of indole-3-carbinol (I3C) molecules (NBP@mSiO<sub>2</sub>-PEG-cRGD/I3C), an anti-tumor agent derived from food. Mediated by cRGD/integrin αvβ3 interaction, NBP@mSiO<sub>2</sub>-PEG-cRGD/I3C reached breast tumors in a targeted manner. Once irradiated by the near-infrared laser, our nanocarrier exhibited superior photothermal conversion, which not only induced photothermal therapy but also facilitated the release of I3C from NBP@mSiO<sub>2</sub>-PEG-cRGD/I3C within tumor cells to inhibit the activation of proto-oncogenic phosphoinositide 3-kinase (PI3K)-AKT signaling pathway and drive chemotherapy. All these attributes contributed to a satisfactory therapeutic effect toward breast tumors, manifesting in significant inhibition of cell proliferation, promotion of cell apoptosis, and reduction of tumor micro-vessel formation, which led to the efficient inhibition of tumor growth. Collectively, the nanocarrier developed here provided useful insights into the development of multifunctional platforms to effectively combat cancer.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101563"},"PeriodicalIF":8.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387400","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
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Materials Today Bio
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