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MnGA with multiple enzyme-like properties for acute wound healing by reducing oxidative stress and modulating signaling pathways
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2024.101435
Xueting Guo , Wenqi Wang , Liting Lin , Jie Shan , Junyao Zhu , Shipeng Ning , Hanmei Li , Xianwen Wang , Decheng Lu
Nanozymes with specific catalytic activity inhibit inflammation and promote wound healing efficiently and safely. In this work, multifunctional manganese-based nanozymes (MnGA) with antioxidant properties were successfully constructed via a simple coordination reaction in which manganese chloride was used as the manganese source and gallic acid (GA) was used as the ligand solution. MnGA possesses both catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities and a reactive nitrogen species (RNS) scavenging capacity, which enables it to efficiently inhibit the inflammatory response. Specifically, MnGA scavenges superoxide anions and produces H2O2 via SOD-like activity and then consumes H2O2 to convert it to nontoxic H2O and O2 via CAT-like activity, resulting in a cascade of catalytic reactions to scavenge reactive oxygen species (ROS). Moreover, the scavenging of RNS by MnGA can amplify the anti-inflammatory effect in combination with the scavenging of ROS. RNA sequencing of mouse skin tissue further revealed that MnGA significantly reduces inflammation by modulating the nuclear factor kappa-B (NF-κB), Toll-like receptor (TLR), and NOD-like receptor (NLR) signaling pathways and promotes skin regeneration. In summary, MnGA nanocatalysts possess excellent antioxidative and anti-inflammatory properties, highlighting their potential applications in wound healing and inflammation treatment.
{"title":"MnGA with multiple enzyme-like properties for acute wound healing by reducing oxidative stress and modulating signaling pathways","authors":"Xueting Guo ,&nbsp;Wenqi Wang ,&nbsp;Liting Lin ,&nbsp;Jie Shan ,&nbsp;Junyao Zhu ,&nbsp;Shipeng Ning ,&nbsp;Hanmei Li ,&nbsp;Xianwen Wang ,&nbsp;Decheng Lu","doi":"10.1016/j.mtbio.2024.101435","DOIUrl":"10.1016/j.mtbio.2024.101435","url":null,"abstract":"<div><div>Nanozymes with specific catalytic activity inhibit inflammation and promote wound healing efficiently and safely. In this work, multifunctional manganese-based nanozymes (MnGA) with antioxidant properties were successfully constructed via a simple coordination reaction in which manganese chloride was used as the manganese source and gallic acid (GA) was used as the ligand solution. MnGA possesses both catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities and a reactive nitrogen species (RNS) scavenging capacity, which enables it to efficiently inhibit the inflammatory response. Specifically, MnGA scavenges superoxide anions and produces H<sub>2</sub>O<sub>2</sub> via SOD-like activity and then consumes H<sub>2</sub>O<sub>2</sub> to convert it to nontoxic H<sub>2</sub>O and O<sub>2</sub> via CAT-like activity, resulting in a cascade of catalytic reactions to scavenge reactive oxygen species (ROS). Moreover, the scavenging of RNS by MnGA can amplify the anti-inflammatory effect in combination with the scavenging of ROS. RNA sequencing of mouse skin tissue further revealed that MnGA significantly reduces inflammation by modulating the nuclear factor kappa-B (NF-κB), Toll-like receptor (TLR), and NOD-like receptor (NLR) signaling pathways and promotes skin regeneration. In summary, MnGA nanocatalysts possess excellent antioxidative and anti-inflammatory properties, highlighting their potential applications in wound healing and inflammation treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101435"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029153","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
ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy 人体脂肪组织的 ECM 模拟水凝胶模型确定了抗雄激素疗法下前列腺癌-脂肪细胞串联过程中的脂质代谢失调。
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2024.101424
Agathe Bessot , Joan Röhl , Maria Emmerich , Anton Klotz , Akhilandeshwari Ravichandran , Christoph Meinert , David Waugh , Jacqui McGovern , Jenni Gunter , Nathalie Bock
Antiandrogen therapies are effectively used to treat advanced prostate cancer, but eventually cancer adaptation drives unresolved metastatic castration-resistant prostate cancer (mCRPC). Adipose tissue influences metabolic reprogramming in cancer and was proposed as a contributor to therapy resistance. Using extracellular matrix (ECM)-mimicking hydrogel coculture models of human adipocytes and prostate cancer cells, we show that adipocytes from subcutaneous or bone marrow fat have dissimilar responses under the antiandrogen Enzalutamide. We demonstrate that androgen receptor (AR)-dependent cancer cells (LNCaP) are more influenced by human adipocytes than AR-independent cells (C4-2B), with altered lipid metabolism and adipokine secretion. This response changes under Enzalutamide, with increased AR expression and adipogenic and lipogenic genes in cancer cells and decreased lipid content and gene dysregulation associated with insulin resistance in adipocytes. This is in line with the metabolic syndrome that men with mCRPC under Enzalutamide experience. The all-human, all-3D, models presented here provide a significant advance to dissect the role of fat in therapy response for mCRPC.
{"title":"ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy","authors":"Agathe Bessot ,&nbsp;Joan Röhl ,&nbsp;Maria Emmerich ,&nbsp;Anton Klotz ,&nbsp;Akhilandeshwari Ravichandran ,&nbsp;Christoph Meinert ,&nbsp;David Waugh ,&nbsp;Jacqui McGovern ,&nbsp;Jenni Gunter ,&nbsp;Nathalie Bock","doi":"10.1016/j.mtbio.2024.101424","DOIUrl":"10.1016/j.mtbio.2024.101424","url":null,"abstract":"<div><div>Antiandrogen therapies are effectively used to treat advanced prostate cancer, but eventually cancer adaptation drives unresolved metastatic castration-resistant prostate cancer (mCRPC). Adipose tissue influences metabolic reprogramming in cancer and was proposed as a contributor to therapy resistance. Using extracellular matrix (ECM)-mimicking hydrogel coculture models of human adipocytes and prostate cancer cells, we show that adipocytes from subcutaneous or bone marrow fat have dissimilar responses under the antiandrogen Enzalutamide. We demonstrate that androgen receptor (AR)-dependent cancer cells (LNCaP) are more influenced by human adipocytes than AR-independent cells (C4-2B), with altered lipid metabolism and adipokine secretion. This response changes under Enzalutamide, with increased AR expression and adipogenic and lipogenic genes in cancer cells and decreased lipid content and gene dysregulation associated with insulin resistance in adipocytes. This is in line with the metabolic syndrome that men with mCRPC under Enzalutamide experience. The all-human, all-3D, models presented here provide a significant advance to dissect the role of fat in therapy response for mCRPC.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101424"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047184","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-drug loaded chondroitin sulfate embolization beads enhance TACE therapy for HCC by integrating embolization, chemotherapy, and anti-angiogenesis
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2024.101419
Jin-Xin Huang , Rui Yang , Huan Long , Jie Kong , Guo-Qiang Shao , Fei Xiong
Hepatocellular carcinoma (HCC) is a major public health threat due to its high incidence and mortality rates. Transcatheter arterial chemoembolization (TACE), the primary treatment for intermediate-to-advanced hepatocellular carcinoma (HCC), commonly utilizes embolic agents loaded with anthracycline-based cytotoxic drugs. Post-TACE, the hypoxic microenvironment in the tumor induced by embolization stimulates the formation of new blood vessels, potentially leading to revascularization and diminishing TACE's efficacy. In clinical practice, combined therapy for liver cancer using TACE and oral targeted drugs often encounters the limitation that targeted drugs cannot efficiently reach the tumor site following TACE. We have developed chondroitin sulfate microspheres (CMs) capable of encapsulating both the cytotoxic drug idarubicin (Ida) and the vascular inhibitor Lenvatinib (Len), thereby achieving a triple therapeutic effect on liver cancer: embolic starvation, drug toxicity, and efficient inhibition of neovascularization.
{"title":"Dual-drug loaded chondroitin sulfate embolization beads enhance TACE therapy for HCC by integrating embolization, chemotherapy, and anti-angiogenesis","authors":"Jin-Xin Huang ,&nbsp;Rui Yang ,&nbsp;Huan Long ,&nbsp;Jie Kong ,&nbsp;Guo-Qiang Shao ,&nbsp;Fei Xiong","doi":"10.1016/j.mtbio.2024.101419","DOIUrl":"10.1016/j.mtbio.2024.101419","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a major public health threat due to its high incidence and mortality rates. Transcatheter arterial chemoembolization (TACE), the primary treatment for intermediate-to-advanced hepatocellular carcinoma (HCC), commonly utilizes embolic agents loaded with anthracycline-based cytotoxic drugs. Post-TACE, the hypoxic microenvironment in the tumor induced by embolization stimulates the formation of new blood vessels, potentially leading to revascularization and diminishing TACE's efficacy. In clinical practice, combined therapy for liver cancer using TACE and oral targeted drugs often encounters the limitation that targeted drugs cannot efficiently reach the tumor site following TACE. We have developed chondroitin sulfate microspheres (CMs) capable of encapsulating both the cytotoxic drug idarubicin (Ida) and the vascular inhibitor Lenvatinib (Len), thereby achieving a triple therapeutic effect on liver cancer: embolic starvation, drug toxicity, and efficient inhibition of neovascularization.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101419"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023881","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
Inactivation of antibiotic resistant bacteria by nitrogen-doped carbon quantum dots through spontaneous generation of intracellular and extracellular reactive oxygen species
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2024.101428
Weibo Xia , Zixia Wu , Bingying Hou , Zhang Cheng , Dechuang Bi , Luya Chen , Wei Chen , Heyang Yuan , Leo H. Koole , Lei Qi
The widespread antibiotic resistance has called for alternative antimicrobial agents. Carbon nanomaterials, especially carbon quantum dots (CQDs), may be promising alternatives due to their desirable physicochemical properties and potential antimicrobial activity, but their antimicrobial mechanism remains to be investigated. In this study, nitrogen-doped carbon quantum dots (N-CQDs) were synthesized to inactivate antibiotic-resistant bacteria and treat bacterial keratitis. N-CQDs synthesized via a facile hydrothermal approach displayed a uniform particle size of less than 10 nm, featuring a graphitic carbon structure and functional groups including -OH and -NH2. The N-CQDs demonstrated antimicrobial activity against Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus, which was both dose- and time-dependent, reducing the survival rate to below 1 %. The antimicrobial activity was confirmed by live/dead staining. In in vivo studies, the N-CQDs were more efficient in treating drug-resistant bacterial keratitis and reducing corneal damage compared to the common antibiotic levofloxacin. The N-CQDs were shown to generate intracellular and extracellular ROS, which potentially caused oxidative stress, membrane disruption, and cell death. This antimicrobial mechanism was supported by scanning and transmission electron microscopy, significant regulation of genes related to oxidative stress, and increased protein and lactate dehydrogenase leakage. This study has provided insight into the development, application, and mechanism of N-CQDs in antimicrobial applications.
{"title":"Inactivation of antibiotic resistant bacteria by nitrogen-doped carbon quantum dots through spontaneous generation of intracellular and extracellular reactive oxygen species","authors":"Weibo Xia ,&nbsp;Zixia Wu ,&nbsp;Bingying Hou ,&nbsp;Zhang Cheng ,&nbsp;Dechuang Bi ,&nbsp;Luya Chen ,&nbsp;Wei Chen ,&nbsp;Heyang Yuan ,&nbsp;Leo H. Koole ,&nbsp;Lei Qi","doi":"10.1016/j.mtbio.2024.101428","DOIUrl":"10.1016/j.mtbio.2024.101428","url":null,"abstract":"<div><div>The widespread antibiotic resistance has called for alternative antimicrobial agents. Carbon nanomaterials, especially carbon quantum dots (CQDs), may be promising alternatives due to their desirable physicochemical properties and potential antimicrobial activity, but their antimicrobial mechanism remains to be investigated. In this study, nitrogen-doped carbon quantum dots (N-CQDs) were synthesized to inactivate antibiotic-resistant bacteria and treat bacterial keratitis. N-CQDs synthesized via a facile hydrothermal approach displayed a uniform particle size of less than 10 nm, featuring a graphitic carbon structure and functional groups including -OH and -NH<sub>2</sub>. The N-CQDs demonstrated antimicrobial activity against <em>Staphylococcus aureus (S. aureus)</em> and methicillin-resistant <em>S. aureus</em>, which was both dose- and time-dependent, reducing the survival rate to below 1 %. The antimicrobial activity was confirmed by live/dead staining. In <em>in vivo</em> studies, the N-CQDs were more efficient in treating drug-resistant bacterial keratitis and reducing corneal damage compared to the common antibiotic levofloxacin. The N-CQDs were shown to generate intracellular and extracellular ROS, which potentially caused oxidative stress, membrane disruption, and cell death. This antimicrobial mechanism was supported by scanning and transmission electron microscopy, significant regulation of genes related to oxidative stress, and increased protein and lactate dehydrogenase leakage. This study has provided insight into the development, application, and mechanism of N-CQDs in antimicrobial applications.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101428"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029152","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
Conversion therapy strategy: A novel GPC3-targeted multimodal organic phototheranostics platform for mid-late-stage hepatocellular carcinoma
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2024.101442
Fan Wu , Xin Kuang , Sanlin Deng , Shuo Qi , Jian Xiong , Bibo Zhao , Chuanfu Li , Senyou Tan , Qiang Kang , Hao Xiao , Xiaofeng Tan , Gui-long Wu , Qinglai Yang , Guodong Chen
Hepatocellular carcinoma (HCC) is typically diagnosed at intermediate to advanced stage, making surgical treatment unfeasible. Conversion therapy aims to reduce tumor stage, improve hepatic resection feasibility, and lower recurrence rates. Since traditional therapies are often accompanied by uncertainty of efficacy, there is an urgent need to explore new treatment strategies. Near-infrared phototheranostics technology provides a new way for HCC diagnosis and treatment by its excellent optical properties. However, complex preparation and poor biocompatibility of phototheranostics probes limit clinical application. In this study, we developed a fluorescence/magnetic resonance dual-modality imaging (FLI/MRI) as well as photothermal/photodynamic therapy (PTT/PDT) GPC3-targeted multifunctional phototheranostics probe, IR820-GPC3-Gd NPs (IGD NPs), to improve the efficiency of conversion therapy for HCC. The IGD NPs were simply prepared with the IR820 as the core. Conjugating the HCC-specific targeting molecule GPC3 peptide and the MRI agent DOTA-Gd through click chemistry. IGD NPs target HCC cells through GPC3, releasing heat and reactive oxygen species (ROS) under noninvasive 808 nm laser irradiation to reduce tumor size and achieve downstaging. High-sensitivity FLI/MRI precisely delineates tumor boundaries, providing real-time surgical navigation and prognosis assessment. This novel probe offers a feasible and effective treatment option for advanced HCC.
肝细胞癌(HCC)通常被诊断为中晚期,因此手术治疗不可行。转化疗法旨在减少肿瘤分期、提高肝切除术的可行性并降低复发率。由于传统疗法往往存在疗效不确定的问题,因此迫切需要探索新的治疗策略。近红外光热疗法技术以其优异的光学特性为 HCC 诊断和治疗提供了一条新途径。然而,光热效应探针制备复杂、生物相容性差,限制了其临床应用。在这项研究中,我们开发了一种荧光/磁共振双模态成像(FLI/MRI)以及光热/光动力疗法(PTT/PDT)GPC3靶向多功能光otheranostics探针--IR820-GPC3-Gd NPs(IGD NPs),以提高HCC转化疗法的效率。IGD NPs以IR820为核心进行简单制备。通过点击化学将 HCC 特异性靶向分子 GPC3 肽与磁共振成像剂 DOTA-Gd 共轭。IGD NPs 通过 GPC3 靶向 HCC 细胞,在无创 808 纳米激光照射下释放热量和活性氧 (ROS),从而缩小肿瘤体积并实现降期。高灵敏度 FLI/MRI 可精确划分肿瘤边界,提供实时手术导航和预后评估。这种新型探针为晚期 HCC 提供了一种可行而有效的治疗方案。
{"title":"Conversion therapy strategy: A novel GPC3-targeted multimodal organic phototheranostics platform for mid-late-stage hepatocellular carcinoma","authors":"Fan Wu ,&nbsp;Xin Kuang ,&nbsp;Sanlin Deng ,&nbsp;Shuo Qi ,&nbsp;Jian Xiong ,&nbsp;Bibo Zhao ,&nbsp;Chuanfu Li ,&nbsp;Senyou Tan ,&nbsp;Qiang Kang ,&nbsp;Hao Xiao ,&nbsp;Xiaofeng Tan ,&nbsp;Gui-long Wu ,&nbsp;Qinglai Yang ,&nbsp;Guodong Chen","doi":"10.1016/j.mtbio.2024.101442","DOIUrl":"10.1016/j.mtbio.2024.101442","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is typically diagnosed at intermediate to advanced stage, making surgical treatment unfeasible. Conversion therapy aims to reduce tumor stage, improve hepatic resection feasibility, and lower recurrence rates. Since traditional therapies are often accompanied by uncertainty of efficacy, there is an urgent need to explore new treatment strategies. Near-infrared phototheranostics technology provides a new way for HCC diagnosis and treatment by its excellent optical properties. However, complex preparation and poor biocompatibility of phototheranostics probes limit clinical application. In this study, we developed a fluorescence/magnetic resonance dual-modality imaging (FLI/MRI) as well as photothermal/photodynamic therapy (PTT/PDT) GPC3-targeted multifunctional phototheranostics probe, IR820-GPC3-Gd NPs (IGD NPs), to improve the efficiency of conversion therapy for HCC. The IGD NPs were simply prepared with the IR820 as the core. Conjugating the HCC-specific targeting molecule GPC3 peptide and the MRI agent DOTA-Gd through click chemistry. IGD NPs target HCC cells through GPC3, releasing heat and reactive oxygen species (ROS) under noninvasive 808 nm laser irradiation to reduce tumor size and achieve downstaging. High-sensitivity FLI/MRI precisely delineates tumor boundaries, providing real-time surgical navigation and prognosis assessment. This novel probe offers a feasible and effective treatment option for advanced HCC.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101442"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047167","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 novel nanocarrier based on natural polyphenols enhancing gemcitabine sensitization ability for improved pancreatic cancer therapy efficiency
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2025.101463
Yuman Dong , Jieru Li , Yiwei Dai , Xinyu Zhang , Xiangyan Jiang , Tao Wang , Bin Zhao , Wenbo Liu , Haonan Sun , Pengcheng Du , Long Qin , Zuoyi Jiao
Pancreatic cancer (PC) is a highly lethal malignancy with rapid progression and poor prognosis. Despite the widespread use of gemcitabine (Gem)-based chemotherapy as the first-line treatment for PC, its efficacy is often compromised by significant drug resistance. 1,2,3,4,6-Pentagaloyl glucose (PGG), a natural polyphenol, has demonstrated potential in sensitizing PC cells to Gem. However, its clinical application is limited by poor water solubility and bioavailability. In this study, we developed a novel PGG-based nanocarrier (FP) using a straightforward, one-step self-assembly method with Pluronic F127 and PGG. Our results showed that FP induced DNA damage and immunogenic cell death (ICD) in both in vitro cell experiments and patient-derived organoid models, exhibiting potent anti-tumor effects. Furthermore, in mouse KPC and PDX models, FP, when combined with Gem, showed enhanced Gem sensitization compared to pure PGG, largely due to increased DNA damage and ICD induction. These findings demonstrate the potential of FP to improve the stability and utilization of PGG as effective Gem sensitizers in the treatment of pancreatic cancer, providing a promising pathway for clinical application and translational research.
{"title":"A novel nanocarrier based on natural polyphenols enhancing gemcitabine sensitization ability for improved pancreatic cancer therapy efficiency","authors":"Yuman Dong ,&nbsp;Jieru Li ,&nbsp;Yiwei Dai ,&nbsp;Xinyu Zhang ,&nbsp;Xiangyan Jiang ,&nbsp;Tao Wang ,&nbsp;Bin Zhao ,&nbsp;Wenbo Liu ,&nbsp;Haonan Sun ,&nbsp;Pengcheng Du ,&nbsp;Long Qin ,&nbsp;Zuoyi Jiao","doi":"10.1016/j.mtbio.2025.101463","DOIUrl":"10.1016/j.mtbio.2025.101463","url":null,"abstract":"<div><div>Pancreatic cancer (PC) is a highly lethal malignancy with rapid progression and poor prognosis. Despite the widespread use of gemcitabine (Gem)-based chemotherapy as the first-line treatment for PC, its efficacy is often compromised by significant drug resistance. 1,2,3,4,6-Pentagaloyl glucose (PGG), a natural polyphenol, has demonstrated potential in sensitizing PC cells to Gem. However, its clinical application is limited by poor water solubility and bioavailability. In this study, we developed a novel PGG-based nanocarrier (FP) using a straightforward, one-step self-assembly method with Pluronic F127 and PGG. Our results showed that FP induced DNA damage and immunogenic cell death (ICD) in both <em>in vitro</em> cell experiments and patient-derived organoid models, exhibiting potent anti-tumor effects. Furthermore, in mouse KPC and PDX models, FP, when combined with Gem, showed enhanced Gem sensitization compared to pure PGG, largely due to increased DNA damage and ICD induction. These findings demonstrate the potential of FP to improve the stability and utilization of PGG as effective Gem sensitizers in the treatment of pancreatic cancer, providing a promising pathway for clinical application and translational research.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101463"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047054","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 motion-responsive injectable lubricative hydrogel for efficient Achilles tendon adhesion prevention
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2025.101458
Shujie Cheng , Jihong Yang , Jianguo Song , Xin Cao , Bowen Zhou , Lan Yang , Chong Li , Yi Wang
Achilles tendon is a motor organ that is prone to tissue adhesion during its repair process after rupture. Therefore, developing motion-responsive and anti-adhesive biomaterials is an important need for the repair of Achilles tendon rupture. Here, we report an injectable lubricative hydrogel (ILH) based on hydration lubrication mechanism, which is also motion-responsive based on sol-gel reversible transmission. The lubrication performance is achieved by zwitterionic polymers as we previously proved, and the sol-gel reversible transmission is enabled by dynamic disulfide bonds. Firstly, ILH was proved to be successfully prepared and lubricated as well as sol-gel reversible via FTIR characterization, rheological measurement and tribological tests. Then, in vitro cell experiments and coagulation tests demonstrated the optimal cytocompatibility and hemocompatibility of ILH. To evaluate the potential of ILH's biofunction in vivo, SD rats' Achilles tendon rupture & repair model was established. The animal experiments' results showed that ILH significantly prevented tendon adhesion and thus promote tendon healing by inhibiting TGFβ1-Smad2/3 pathway. We believe this work will open a new horizon for tendon adhesion-free repair.
{"title":"A motion-responsive injectable lubricative hydrogel for efficient Achilles tendon adhesion prevention","authors":"Shujie Cheng ,&nbsp;Jihong Yang ,&nbsp;Jianguo Song ,&nbsp;Xin Cao ,&nbsp;Bowen Zhou ,&nbsp;Lan Yang ,&nbsp;Chong Li ,&nbsp;Yi Wang","doi":"10.1016/j.mtbio.2025.101458","DOIUrl":"10.1016/j.mtbio.2025.101458","url":null,"abstract":"<div><div>Achilles tendon is a motor organ that is prone to tissue adhesion during its repair process after rupture. Therefore, developing motion-responsive and anti-adhesive biomaterials is an important need for the repair of Achilles tendon rupture. Here, we report an injectable lubricative hydrogel (ILH) based on hydration lubrication mechanism, which is also motion-responsive based on sol-gel reversible transmission. The lubrication performance is achieved by zwitterionic polymers as we previously proved, and the sol-gel reversible transmission is enabled by dynamic disulfide bonds. Firstly, ILH was proved to be successfully prepared and lubricated as well as sol-gel reversible via FTIR characterization, rheological measurement and tribological tests. Then, in vitro cell experiments and coagulation tests demonstrated the optimal cytocompatibility and hemocompatibility of ILH. To evaluate the potential of ILH's biofunction <em>in vivo</em>, SD rats' Achilles tendon rupture &amp; repair model was established. The animal experiments' results showed that ILH significantly prevented tendon adhesion and thus promote tendon healing by inhibiting TGFβ1-Smad2/3 pathway. We believe this work will open a new horizon for tendon adhesion-free repair.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101458"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047138","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
DNA nanotechnology-based strategies for gastric cancer diagnosis and therapy
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2025.101459
Congcong Li, Tongyang Xu, Guopeng Hou, Yin Wang, Qinrui Fu
Gastric cancer (GC) is a formidable adversary in the field of oncology. The low early diagnosis rate of GC results in a low overall survival rate. Therefore, early accurate diagnosis and effective treatment are the key to reduce the mortality of GC. With the advent of nanotechnology, researchers continue to explore new possibilities for accurate diagnosis and effective treatment. One such breakthrough is the application of DNA nanotechnology. In this paper, the application of exciting DNA nanomaterials in the diagnosis and treatment of GC is discussed in depth. Firstly, the biomarkers related to GC and the diagnostic strategies related to DNA nanotechnology are summarized. Second, the latest research progress of DNA nanomaterials in the GC targeted therapy are summarized. Finally, the challenges and opportunities of DNA nanomaterials in the research and clinical application of GC are prospected.
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引用次数: 0
Localized propranolol delivery from a copper-loaded hydrogel for enhancing infected burn wound healing via adrenergic β-receptor blockade
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2024.101417
Wenzhe Sun , Hongwei Lu , Pengqin Zhang, Lian Zeng, Bing Ye, Yi Xu, Jianan Chen, Peiran Xue, Jialin Yu, Kaifang Chen, Bin Wu, Xiao Lv, Xiaodong Guo, Yanzhen Qu
Severe burn injuries immediately trigger a sustained systemic and local stress response. During this process, the sympathetic nervous system releases large amounts of catecholamines, which bind to β-adrenergic receptors (β-AR) on cell membranes, negatively affecting skin regeneration. Additionally, recurrent bacterial infections make burn wounds difficult to treat, posing significant and ongoing challenges to burn care. To address these challenges, we pioneered the study of locally delivered propranolol for burn wound treatment, revealing its ability to antagonize norepinephrine (NE) and regulate the sympathetic nervous system. In this study, a Cu2⁺-loaded anti-sympathetic hydrogel (copper ion cross-linked propranolol@gelatin/alginate, PNL@GA-Cu) was developed to remodel the challenging neuromodulatory microenvironment and accelerate the repair of the infected burn wound. The hydrogel system releases Cu2⁺ and propranolol simultaneously during degradation, synergistically acting on local wound tissue. Cu2⁺ exhibits dual effects of antibacterial activity and promoting angiogenesis, effectively killing Staphylococcus aureus and Escherichia coli while enhancing the expression of angiogenesis-related genes (CD31, VEGF). Meanwhile, propranolol can counteract the inhibitory effects of NE simulated chronic stress microenvironment on angiogenesis and mitigate sympathetic nerve innervation during the early stages of wound healing. Finally, the PNL@GA-Cu hydrogel significantly promoted the repair of third-degree full-thickness burns in SD rats. Approaches targeting the neural microenvironment for burn wound treatment has not been previously addressed in the literature. The anti-sympathetic PNL@GA-Cu hydrogel offers a promising strategy for treating infected burn wounds. Remodeling the neuromodulatory microenvironment could be an emerging strategy in tissue engineering.
{"title":"Localized propranolol delivery from a copper-loaded hydrogel for enhancing infected burn wound healing via adrenergic β-receptor blockade","authors":"Wenzhe Sun ,&nbsp;Hongwei Lu ,&nbsp;Pengqin Zhang,&nbsp;Lian Zeng,&nbsp;Bing Ye,&nbsp;Yi Xu,&nbsp;Jianan Chen,&nbsp;Peiran Xue,&nbsp;Jialin Yu,&nbsp;Kaifang Chen,&nbsp;Bin Wu,&nbsp;Xiao Lv,&nbsp;Xiaodong Guo,&nbsp;Yanzhen Qu","doi":"10.1016/j.mtbio.2024.101417","DOIUrl":"10.1016/j.mtbio.2024.101417","url":null,"abstract":"<div><div>Severe burn injuries immediately trigger a sustained systemic and local stress response. During this process, the sympathetic nervous system releases large amounts of catecholamines, which bind to β-adrenergic receptors (β-AR) on cell membranes, negatively affecting skin regeneration. Additionally, recurrent bacterial infections make burn wounds difficult to treat, posing significant and ongoing challenges to burn care. To address these challenges, we pioneered the study of locally delivered propranolol for burn wound treatment, revealing its ability to antagonize norepinephrine (NE) and regulate the sympathetic nervous system. In this study, a Cu<sup>2</sup>⁺-loaded anti-sympathetic hydrogel (copper ion cross-linked propranolol@gelatin/alginate, PNL@GA-Cu) was developed to remodel the challenging neuromodulatory microenvironment and accelerate the repair of the infected burn wound. The hydrogel system releases Cu<sup>2</sup>⁺ and propranolol simultaneously during degradation, synergistically acting on local wound tissue. Cu<sup>2</sup>⁺ exhibits dual effects of antibacterial activity and promoting angiogenesis, effectively killing <em>Staphylococcus aureus</em> and <em>Escherichia coli</em> while enhancing the expression of angiogenesis-related genes (CD31, VEGF). Meanwhile, propranolol can counteract the inhibitory effects of NE simulated chronic stress microenvironment on angiogenesis and mitigate sympathetic nerve innervation during the early stages of wound healing. Finally, the PNL@GA-Cu hydrogel significantly promoted the repair of third-degree full-thickness burns in SD rats. Approaches targeting the neural microenvironment for burn wound treatment has not been previously addressed in the literature. The anti-sympathetic PNL@GA-Cu hydrogel offers a promising strategy for treating infected burn wounds. Remodeling the neuromodulatory microenvironment could be an emerging strategy in tissue engineering.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101417"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080600","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
AIEgen-self-assembled nanoparticles with anti-PD-L1 antibody functionalization realize enhanced synergistic photodynamic therapy and immunotherapy against malignant melanoma 具有抗pd - l1抗体功能化的aiegen自组装纳米颗粒实现了对恶性黑色素瘤增强的协同光动力治疗和免疫治疗。
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-02-01 DOI: 10.1016/j.mtbio.2024.101387
Lu Li , Qing Xu , Xiuzhen Zhang , Yuan Jiang , La Zhang , Jiao Guo , Haichuan Liu , Bin Jiang , Shenglong Li , Qiling Peng , Ning Jiang , Jianwei Wang
Immune checkpoint inhibitors (ICIs) become integral in clinical practice, yet their application in cancer therapy is constrained by low overall response rates and the primary resistance of cancers to ICIs. Herein, this study proposes aggregation-induced emission (AIE)-based nanoparticles (NPs) for a more effective and synergistic approach combining immunotherapy and photodynamic therapy (PDT) to achieve higher responses than anti-PD-L1 monotherapy. The TBP@aPD-L1 NPs are constructed by functionalizing azide group-modified TBP-2 (TBP-N3) with anti-PD-L1 antibodies via the DBCO-S-S-PEG2000-COOH linker. The anti-PD-L1 target the tumor cells and promote the TBP-N3 accumulation in tumors for enhanced PDT. Notably, the TBP-N3, featuring aggregation-induced emission, boosts reactive oxygen species (ROS) generation through both type I and type II processes for enhanced PDT. The TBP@aPD-L1-mediated PDT induces more powerful effects of direct tumor cell-killing and further elicits effective immunogenic cell death (ICD), which exerts anti-tumor immunity by activating T cells for ICI treatment and reshapes the tumor immune microenvironment (TIME), thereby enhancing the efficacy of PD-L1 blockade of anti-PD-L1. Consequently, TBP@aPD-L1 NPs demonstrated significantly enhanced inhibition of tumor growth in the mouse model of malignant melanoma (MM). Our NPs act as a facile and effective drug delivery platform for enhanced immunotherapy combined with enhanced PDT in treating MM.
免疫检查点抑制剂(ICIs)在临床实践中不可或缺,但其在癌症治疗中的应用受到总体反应率低和癌症对ICIs的原发性耐药的限制。在此,本研究提出基于聚集诱导发射(AIE)的纳米颗粒(NPs)作为一种更有效和协同的方法,将免疫疗法和光动力疗法(PDT)结合起来,以获得比抗pd - l1单药更高的疗效。TBP@aPD-L1 NPs是通过DBCO-S-S-PEG2000-COOH连接器将叠氮化物基团修饰的TBP-2 (TBP-N3)与抗pd - l1抗体功能化而构建的。抗pd - l1靶向肿瘤细胞,促进TBP-N3在肿瘤中的积累,增强PDT。值得注意的是,TBP-N3具有聚集诱导发射的特点,可以通过I型和II型过程促进活性氧(ROS)的产生,从而增强PDT。TBP@aPD-L1-mediated PDT诱导更强大的直接杀伤肿瘤细胞的作用,并进一步诱导有效的免疫原性细胞死亡(ICD),通过激活T细胞进行ICI治疗发挥抗肿瘤免疫作用,重塑肿瘤免疫微环境(TIME),从而增强PD-L1阻断抗PD-L1的功效。因此,TBP@aPD-L1 NPs在恶性黑色素瘤(MM)小鼠模型中显示出显著增强的肿瘤生长抑制作用。我们的NPs作为一种简单有效的药物输送平台,用于增强免疫疗法联合增强PDT治疗MM。
{"title":"AIEgen-self-assembled nanoparticles with anti-PD-L1 antibody functionalization realize enhanced synergistic photodynamic therapy and immunotherapy against malignant melanoma","authors":"Lu Li ,&nbsp;Qing Xu ,&nbsp;Xiuzhen Zhang ,&nbsp;Yuan Jiang ,&nbsp;La Zhang ,&nbsp;Jiao Guo ,&nbsp;Haichuan Liu ,&nbsp;Bin Jiang ,&nbsp;Shenglong Li ,&nbsp;Qiling Peng ,&nbsp;Ning Jiang ,&nbsp;Jianwei Wang","doi":"10.1016/j.mtbio.2024.101387","DOIUrl":"10.1016/j.mtbio.2024.101387","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) become integral in clinical practice, yet their application in cancer therapy is constrained by low overall response rates and the primary resistance of cancers to ICIs. Herein, this study proposes aggregation-induced emission (AIE)-based nanoparticles (NPs) for a more effective and synergistic approach combining immunotherapy and photodynamic therapy (PDT) to achieve higher responses than anti-PD-L1 monotherapy. The TBP@aPD-L1 NPs are constructed by functionalizing azide group-modified TBP-2 (TBP-N<sub>3</sub>) with anti-PD-L1 antibodies via the DBCO-S-S-PEG<sub>2000</sub>-COOH linker. The anti-PD-L1 target the tumor cells and promote the TBP-N<sub>3</sub> accumulation in tumors for enhanced PDT. Notably, the TBP-N<sub>3</sub>, featuring aggregation-induced emission, boosts reactive oxygen species (ROS) generation through both type I and type II processes for enhanced PDT. The TBP@aPD-L1-mediated PDT induces more powerful effects of direct tumor cell-killing and further elicits effective immunogenic cell death (ICD), which exerts anti-tumor immunity by activating T cells for ICI treatment and reshapes the tumor immune microenvironment (TIME), thereby enhancing the efficacy of PD-L1 blockade of anti-PD-L1. Consequently, TBP@aPD-L1 NPs demonstrated significantly enhanced inhibition of tumor growth in the mouse model of malignant melanoma (MM). Our NPs act as a facile and effective drug delivery platform for enhanced immunotherapy combined with enhanced PDT in treating MM.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"30 ","pages":"Article 101387"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914441","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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