Biomaterials最新文献_第2页

Ultrasound-triggered lysosomal alkalinization to block autophagy in tumor therapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-08 DOI: 10.1016/j.biomaterials.2025.123250

Yong Liu , Bowen Li , Run Yang , Chenxu Shang , Yang Bai , Bin Zheng , Liang Zhao

Lysosomes play a crucial role in regulating cancer progression and drug resistance. However, there is a pressing need for the development of drugs that can safely and effectively modulate the pH of cancerous lysosomes in a controlled manner. In this study, we propose a novel strategy for lysosomal alkalinization triggered by piezoelectricity. Our findings indicate that the electrons generated by (BaTiO₃/Zr/Ca) BCZT under sonication effectively alkalinize the lysosomes. Molecular dynamics simulations further demonstrate that alterations in lysosomal pH lead to modifications in the conformation of V-ATPase (proton pump), enhancing its interaction with sodium ions while partially excluding hydrogen ions from entering the lysosomes. This mechanism helps maintain lysosomal alkalization, resulting in reduced hydrolase activity and preventing the degradation of proteins and damaged organelles. The accumulation of nanoparticles within the lysosomes causes swelling and gradual destruction of the lysosomal membrane. Consequently, this lysosomal dysfunction hampers the fusion with autophagosomes, inhibiting autophagy in tumor cells and promoting apoptosis in various tumor types. Our strategy significantly inhibited tumor volume growth in mice during animal studies. In conclusion, our piezoelectric-triggered lysosomal alkalinization strategy holds promise for innovative breakthroughs in the treatment of multiple cancers.

{"title":"Ultrasound-triggered lysosomal alkalinization to block autophagy in tumor therapy","authors":"Yong Liu , Bowen Li , Run Yang , Chenxu Shang , Yang Bai , Bin Zheng , Liang Zhao","doi":"10.1016/j.biomaterials.2025.123250","DOIUrl":"10.1016/j.biomaterials.2025.123250","url":null,"abstract":"<div><div>Lysosomes play a crucial role in regulating cancer progression and drug resistance. However, there is a pressing need for the development of drugs that can safely and effectively modulate the pH of cancerous lysosomes in a controlled manner. In this study, we propose a novel strategy for lysosomal alkalinization triggered by piezoelectricity. Our findings indicate that the electrons generated by (BaTiO<sub>3</sub>/Zr/Ca) BCZT under sonication effectively alkalinize the lysosomes. Molecular dynamics simulations further demonstrate that alterations in lysosomal pH lead to modifications in the conformation of V-ATPase (proton pump), enhancing its interaction with sodium ions while partially excluding hydrogen ions from entering the lysosomes. This mechanism helps maintain lysosomal alkalization, resulting in reduced hydrolase activity and preventing the degradation of proteins and damaged organelles. The accumulation of nanoparticles within the lysosomes causes swelling and gradual destruction of the lysosomal membrane. Consequently, this lysosomal dysfunction hampers the fusion with autophagosomes, inhibiting autophagy in tumor cells and promoting apoptosis in various tumor types. Our strategy significantly inhibited tumor volume growth in mice during animal studies. In conclusion, our piezoelectric-triggered lysosomal alkalinization strategy holds promise for innovative breakthroughs in the treatment of multiple cancers.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123250"},"PeriodicalIF":12.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600509","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

Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-06 DOI: 10.1016/j.biomaterials.2025.123238

Anna Y. Lynn , Kwangsoo Shin , David A. Eaton , Micky Rose , Xianzhi Zhang , Madalina Ene , Julian Grundler , Emily Deschenes , Rachel Rivero , Laura G. Bracaglia , Peter M. Glazer , David H. Stitelman , W. Mark Saltzman

When exposed to the biological environment, nanoparticles (NPs) form a protein corona that influences delivery profile. We present a study of protein corona formation and NP biodistribution in amniotic fluid (AF) for poly(lactic-co-glycolic acid) (PLGA) and poly(lactic-acid) (PLA) NPs, with and without polyethylene glycol (PEG), as well as poly(amine-co-ester)-PEG (PACE-PEG) NPs. The presence of surface PEG and polyvinyl alcohol (PVA) were characterized to investigate surfactant role in determining protein corona formation. The surface density of PEG groups demonstrated an inverse correlation with the total amount of protein surface adsorption. All PEGylated NPs exhibited a dense brush conformation and demonstrated higher levels of stability in AF than non-PEGylated NPs. The protein corona composition varied by core polymer, while the amount of protein adsorption varied by PEGylation status. In A549 cells, in vitro cellular association of each NP type correlated with the amount of albumin that was found in the protein corona. In vivo, only PEGylated NPs were able successfully distribute to fetal organs, likely due to the enhanced stability imparted by PEG. PLGA-PEG and PACE-PEG NPs had both high levels of albumin in the protein corona and high biodistribution to the fetal lung, consistent with the association with lung cells in vitro. PLA-PEG NPs distributed exclusively to the fetal bowel, which we propose is associated with known gastrointestinal targeting keratin proteins. By furthering our understanding of polymeric NP behavior in AF, this novel study provides a basis for optimization of intra-amniotic NP delivery systems targeting congenital pulmonary and gastrointestinal diseases.

{"title":"Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery","authors":"Anna Y. Lynn , Kwangsoo Shin , David A. Eaton , Micky Rose , Xianzhi Zhang , Madalina Ene , Julian Grundler , Emily Deschenes , Rachel Rivero , Laura G. Bracaglia , Peter M. Glazer , David H. Stitelman , W. Mark Saltzman","doi":"10.1016/j.biomaterials.2025.123238","DOIUrl":"10.1016/j.biomaterials.2025.123238","url":null,"abstract":"<div><div>When exposed to the biological environment, nanoparticles (NPs) form a protein corona that influences delivery profile. We present a study of protein corona formation and NP biodistribution in amniotic fluid (AF) for poly(lactic-co-glycolic acid) (PLGA) and poly(lactic-acid) (PLA) NPs, with and without polyethylene glycol (PEG), as well as poly(amine-co-ester)-PEG (PACE-PEG) NPs. The presence of surface PEG and polyvinyl alcohol (PVA) were characterized to investigate surfactant role in determining protein corona formation. The surface density of PEG groups demonstrated an inverse correlation with the total amount of protein surface adsorption. All PEGylated NPs exhibited a dense brush conformation and demonstrated higher levels of stability in AF than non-PEGylated NPs. The protein corona composition varied by core polymer, while the amount of protein adsorption varied by PEGylation status. In A549 cells, <em>in vitro</em> cellular association of each NP type correlated with the amount of albumin that was found in the protein corona. <em>In vivo</em>, only PEGylated NPs were able successfully distribute to fetal organs, likely due to the enhanced stability imparted by PEG. PLGA-PEG and PACE-PEG NPs had both high levels of albumin in the protein corona and high biodistribution to the fetal lung, consistent with the association with lung cells <em>in vitro</em>. PLA-PEG NPs distributed exclusively to the fetal bowel, which we propose is associated with known gastrointestinal targeting keratin proteins. By furthering our understanding of polymeric NP behavior in AF, this novel study provides a basis for optimization of intra-amniotic NP delivery systems targeting congenital pulmonary and gastrointestinal diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123238"},"PeriodicalIF":12.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579547","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

Ultrasound-activated piezoelectric heterojunction drives nanozyme catalysis to induce bacterial cuproptosis-like death and promote bone vascularization and osseointegration

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-05 DOI: 10.1016/j.biomaterials.2025.123249

Longhai Qiu , Sushuang Ma , Ren Yang , Dengwen Zheng , Yuliang Huang , Zhengwei Zhu , Sijun Peng , Mei Li , Hua Zhong , Feng Peng

Osteomyelitis is a severe and persistent bone infection that poses significant challenges to clinical treatment, often requiring prolonged antibiotic therapy and invasive procedures. Nanomaterial-based non-antibiotic therapies have emerged as promising alternatives in combating bacterial infections. However, effectively treating osteomyelitis while simultaneously promoting bone repair remains a challenge. Herein, we developed a nanoheterojunction catalytic reactor composed of copper ferrite (CuFe₂O₄) and molybdenum disulfide (MoS₂) quantum dots (CFO@MoS₂), leveraging ultrasound catalysis in combination with copper ions to induce bacterial cuproptosis-like death. Theoretical calculations indicate that the establishment of a heterojunction interface can accelerate oxygen adsorption, inducing electron flow toward oxygen atoms at the interface, thereby enhancing the separation of interface electron-hole pairs. Furthermore, copper ions released from CFO@MoS₂ undergo valence state changes under ultrasound, activating the Fenton reaction and releasing reactive oxygen species to kill bacteria. Gene sequencing shows that CFO@MoS₂, when activated by ultrasound, disrupts bacterial energy synthesis, interferes with bacterial metabolism, and induces copper-related bacterial death. More importantly, the microcurrents generated by ultrasound synergistic with the released copper and iron ions stimulate the expression of angiogenic and osteogenic genes, promoting bone regeneration. The ultrasound-triggered catalytic reaction by CFO@MoS₂ disrupts bacterial homeostasis, accelerates bacterial death, and offers a novel therapeutic strategy for osteomyelitis.

{"title":"Ultrasound-activated piezoelectric heterojunction drives nanozyme catalysis to induce bacterial cuproptosis-like death and promote bone vascularization and osseointegration","authors":"Longhai Qiu , Sushuang Ma , Ren Yang , Dengwen Zheng , Yuliang Huang , Zhengwei Zhu , Sijun Peng , Mei Li , Hua Zhong , Feng Peng","doi":"10.1016/j.biomaterials.2025.123249","DOIUrl":"10.1016/j.biomaterials.2025.123249","url":null,"abstract":"<div><div>Osteomyelitis is a severe and persistent bone infection that poses significant challenges to clinical treatment, often requiring prolonged antibiotic therapy and invasive procedures. Nanomaterial-based non-antibiotic therapies have emerged as promising alternatives in combating bacterial infections. However, effectively treating osteomyelitis while simultaneously promoting bone repair remains a challenge. Herein, we developed a nanoheterojunction catalytic reactor composed of copper ferrite (CuFe<sub>2</sub>O<sub>4</sub>) and molybdenum disulfide (MoS<sub>2</sub>) quantum dots (CFO@MoS<sub>2</sub>), leveraging ultrasound catalysis in combination with copper ions to induce bacterial cuproptosis-like death. Theoretical calculations indicate that the establishment of a heterojunction interface can accelerate oxygen adsorption, inducing electron flow toward oxygen atoms at the interface, thereby enhancing the separation of interface electron-hole pairs. Furthermore, copper ions released from CFO@MoS<sub>2</sub> undergo valence state changes under ultrasound, activating the Fenton reaction and releasing reactive oxygen species to kill bacteria. Gene sequencing shows that CFO@MoS<sub>2</sub>, when activated by ultrasound, disrupts bacterial energy synthesis, interferes with bacterial metabolism, and induces copper-related bacterial death. More importantly, the microcurrents generated by ultrasound synergistic with the released copper and iron ions stimulate the expression of angiogenic and osteogenic genes, promoting bone regeneration. The ultrasound-triggered catalytic reaction by CFO@MoS<sub>2</sub> disrupts bacterial homeostasis, accelerates bacterial death, and offers a novel therapeutic strategy for osteomyelitis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123249"},"PeriodicalIF":12.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579544","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

Reprogrammed glycolysis-induced augmentation of NIR-II excited photodynamic/photothermal therapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-04 DOI: 10.1016/j.biomaterials.2025.123235

Chunbai Xiang , Qihang Ding , Ting Jiang , Yu Liu , Chao Li , Xing Yang , Jia Jia , Jingjing Xiang , Yue Wang , Hui Zhou , Zhiyun Lu , Ping Gong , Jong Seung Kim

Small molecule-based multifunctional optical diagnostic materials have garnered considerable interest due to their highly customizable structures, tunable excited-state properties, and remarkable biocompatibility. We herein report the synthesis of a multifaceted photosensitizer, PPQ-CTPA, which exhibits exceptional efficacy in generating Type I reactive oxygen species (ROS) and thermal energy under near-infrared-II (NIR-II, >1000 nm) laser excitation at 1064 nm, thereby combining photodynamic therapy (PDT) and photothermal therapy (PTT) functionalities. To enhance therapeutic efficacy, we engineered lonidamine (LND) by conjugating it with triphenylphosphonium (TPP) cations, producing LND-TPP. This compound inhibits mitochondrial glycolysis and downregulates heat shock protein 90 (HSP 90) levels in a breast cancer mouse model, potentiating both PDT and PTT. For in vivo applications, PPQ-CTPA and LND-TPP are encapsulated within the amphiphilic polymer DSPE–SS–PEG to obtain PPQ-CTPAL NPs. In breast cancer cell lines, PPQ-CTPAL NPs are decomposed by cellular GSH, simultaneously releasing the dual-functioning photosensitizer PPQ-CTPL and the mitochondria-disrupting agent LND-TPP. Upon 1064 nm laser irradiation, we found that tumor growth in breast cancer mice is effectively restrained by PPQ-CTPAL NPs. This work highlights the synergistic integration of PDT, PTT, and chemotherapy facilitated by NIR-II fluorescence, photoacoustic, and photothermal imaging under 1064 nm irradiation, underscoring the clinical potential of multifunctional phototherapeutic agents.

{"title":"Reprogrammed glycolysis-induced augmentation of NIR-II excited photodynamic/photothermal therapy","authors":"Chunbai Xiang , Qihang Ding , Ting Jiang , Yu Liu , Chao Li , Xing Yang , Jia Jia , Jingjing Xiang , Yue Wang , Hui Zhou , Zhiyun Lu , Ping Gong , Jong Seung Kim","doi":"10.1016/j.biomaterials.2025.123235","DOIUrl":"10.1016/j.biomaterials.2025.123235","url":null,"abstract":"<div><div>Small molecule-based multifunctional optical diagnostic materials have garnered considerable interest due to their highly customizable structures, tunable excited-state properties, and remarkable biocompatibility. We herein report the synthesis of a multifaceted photosensitizer, PPQ-CTPA, which exhibits exceptional efficacy in generating Type I reactive oxygen species (ROS) and thermal energy under near-infrared-II (NIR-II, >1000 nm) laser excitation at 1064 nm, thereby combining photodynamic therapy (PDT) and photothermal therapy (PTT) functionalities. To enhance therapeutic efficacy, we engineered lonidamine (LND) by conjugating it with triphenylphosphonium (TPP) cations, producing LND-TPP. This compound inhibits mitochondrial glycolysis and downregulates heat shock protein 90 (HSP 90) levels in a breast cancer mouse model, potentiating both PDT and PTT. For <em>in vivo</em> applications, PPQ-CTPA and LND-TPP are encapsulated within the amphiphilic polymer DSPE–SS–PEG to obtain <strong>PPQ-CTPAL NPs</strong>. In breast cancer cell lines, <strong>PPQ-CTPAL NPs</strong> are decomposed by cellular GSH, simultaneously releasing the dual-functioning photosensitizer PPQ-CTPL and the mitochondria-disrupting agent LND-TPP. Upon 1064 nm laser irradiation, we found that tumor growth in breast cancer mice is effectively restrained by <strong>PPQ-CTPAL NPs</strong>. This work highlights the synergistic integration of PDT, PTT, and chemotherapy facilitated by NIR-II fluorescence, photoacoustic, and photothermal imaging under 1064 nm irradiation, underscoring the clinical potential of multifunctional phototherapeutic agents.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123235"},"PeriodicalIF":12.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579548","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

Enhanced stem cell-mediated therapeutic immune modulation with zinc oxide nanoparticles in liver regenerative therapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-04 DOI: 10.1016/j.biomaterials.2025.123232

Naeun Park , Kyoung Sub Kim , Sanghee Lee , Jang Ho Choi , Kun Na

Liver regenerative therapy is critical for severe liver damage, including acute liver failure, fibrosis, post-cancer resection recovery, and autoimmune liver diseases, where restoration of liver tissues is essential. Stem cell-based therapies hold significant promise in liver regeneration by modulating immune responses to create a favorable healing microenvironment. However, their clinical efficacy has been limited by challenges such as poor cell engraftment and survival within the hostile injury site. To address these limitations, we developed a zinc oxide-derived nanoparticle (PZnONP) that enhances stem cell proliferation and activation by releasing bioactive Zn²⁺ and reactive oxygen species (ROS). Functionalized PZnONP exhibits pH-responsive behavior and improved dispersibility, enabling a lysosome-specific and sustained release of Zn²⁺ and ROS. Stem cells labeled with PZnONP (ZnBA) demonstrated anti-inflammatory properties, with paracrine effects influencing macrophages and damaged hepatocytes. In murine models of acute and fibrotic liver injury, it effectively migrated to the liver through stem cell homing effects and promoted anti-inflammatory responses by modulating Treg and Th17 cell polarization, as well as M2 and M1 macrophage balance, while reducing collagen synthesis. This study underscores the potential of integrating stem cell-based therapy with nanomedicine to improve regenerative outcomes in liver disease treatment.

{"title":"Enhanced stem cell-mediated therapeutic immune modulation with zinc oxide nanoparticles in liver regenerative therapy","authors":"Naeun Park , Kyoung Sub Kim , Sanghee Lee , Jang Ho Choi , Kun Na","doi":"10.1016/j.biomaterials.2025.123232","DOIUrl":"10.1016/j.biomaterials.2025.123232","url":null,"abstract":"<div><div>Liver regenerative therapy is critical for severe liver damage, including acute liver failure, fibrosis, post-cancer resection recovery, and autoimmune liver diseases, where restoration of liver tissues is essential. Stem cell-based therapies hold significant promise in liver regeneration by modulating immune responses to create a favorable healing microenvironment. However, their clinical efficacy has been limited by challenges such as poor cell engraftment and survival within the hostile injury site. To address these limitations, we developed a zinc oxide-derived nanoparticle (PZnONP) that enhances stem cell proliferation and activation by releasing bioactive Zn<sup>2+</sup> and reactive oxygen species (ROS). Functionalized PZnONP exhibits pH-responsive behavior and improved dispersibility, enabling a lysosome-specific and sustained release of Zn<sup>2+</sup> and ROS. Stem cells labeled with PZnONP (ZnBA) demonstrated anti-inflammatory properties, with paracrine effects influencing macrophages and damaged hepatocytes. In murine models of acute and fibrotic liver injury, it effectively migrated to the liver through stem cell homing effects and promoted anti-inflammatory responses by modulating Treg and Th17 cell polarization, as well as M2 and M1 macrophage balance, while reducing collagen synthesis. This study underscores the potential of integrating stem cell-based therapy with nanomedicine to improve regenerative outcomes in liver disease treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123232"},"PeriodicalIF":12.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579546","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

Hydrogen generators-protected mesenchymal stem cells reverse articular redox imbalance-induced immune dysfunction for osteoarthritis treatment

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-04 DOI: 10.1016/j.biomaterials.2025.123239

Zhou Xu , Ruilong Song , Zhiling Chen , Yu Sun , Yinhe Xia , Haixiang Miao , Weijie Wang , Yuankai Zhang , Xinyi Jiang , Gang Chen

Stem cell therapy has revolutionized the management of osteoarthritis (OA), but the articular dysregulated redox status diminishes cell engraftment efficiency and disrupts immune homeostasis, therefore compromising the overall therapeutic efficacy. Here, we present hydrogen (H₂) generators-backpacked mesenchymal stem cells (MSCs) which preserve the biological functions and survival of transplanted cells and reverse articular immune dysfunction, mitigating OA. Specifically, post systemic transplantation, H₂ generators-laden MSCs home to OA joints, and upon stimulation in acidic OA environment, H₂ produced from the generators remodels articular redox balance, thereby relieving the loss of mitochondrial membrane potential, decreasing cell apoptosis rate, and maintaining pluripotent and paracrine functions of MSCs. Furthermore, the reactive oxygen species scavenging by H₂ in combination with paracrine effects of the MSCs promote macrophage polarization towards the anti-inflammatory M2 phenotype, which contributes to reversing synovial immune disorder. In severe OA model, the backpacked MSCs reduce osteoarthritic degeneration, osteophyte formation and joint inflammation, and promote cartilage regeneration. In sum, our work demonstrates that arming with H₂ generators effectively boosts the therapeutic efficacy of MSCs, which hold great potential for alleviating redox imbalance-related tissue lesions, including but not limited to OA.

{"title":"Hydrogen generators-protected mesenchymal stem cells reverse articular redox imbalance-induced immune dysfunction for osteoarthritis treatment","authors":"Zhou Xu , Ruilong Song , Zhiling Chen , Yu Sun , Yinhe Xia , Haixiang Miao , Weijie Wang , Yuankai Zhang , Xinyi Jiang , Gang Chen","doi":"10.1016/j.biomaterials.2025.123239","DOIUrl":"10.1016/j.biomaterials.2025.123239","url":null,"abstract":"<div><div>Stem cell therapy has revolutionized the management of osteoarthritis (OA), but the articular dysregulated redox status diminishes cell engraftment efficiency and disrupts immune homeostasis, therefore compromising the overall therapeutic efficacy. Here, we present hydrogen (H<sub>2</sub>) generators-backpacked mesenchymal stem cells (MSCs) which preserve the biological functions and survival of transplanted cells and reverse articular immune dysfunction, mitigating OA. Specifically, post systemic transplantation, H<sub>2</sub> generators-laden MSCs home to OA joints, and upon stimulation in acidic OA environment, H<sub>2</sub> produced from the generators remodels articular redox balance, thereby relieving the loss of mitochondrial membrane potential, decreasing cell apoptosis rate, and maintaining pluripotent and paracrine functions of MSCs. Furthermore, the reactive oxygen species scavenging by H<sub>2</sub> in combination with paracrine effects of the MSCs promote macrophage polarization towards the anti-inflammatory M2 phenotype, which contributes to reversing synovial immune disorder. In severe OA model, the backpacked MSCs reduce osteoarthritic degeneration, osteophyte formation and joint inflammation, and promote cartilage regeneration. In sum, our work demonstrates that arming with H<sub>2</sub> generators effectively boosts the therapeutic efficacy of MSCs, which hold great potential for alleviating redox imbalance-related tissue lesions, including but not limited to OA.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123239"},"PeriodicalIF":12.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562901","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

MXene-loaded multifunctional nanoparticles with on-demand controlled antimicrobial and antioxidant capacity for multi-modal treating bacterial prostatitis

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-04 DOI: 10.1016/j.biomaterials.2025.123234

Kailai Liu , Yanyao Gao , Yuchen Zhang , Yunhe Zheng , Jiangchuan He , Yu Huang , Xi Chen , Ruixiao Li , Qiang Fu , Bin Song , He Wang , Lei Wang , Geng Zhang , Ke Wang

Bacterial prostatitis represents a specific form of prostatitis, primarily resulting from bacterial infection and significantly impairing the life quality of patients. In this paper, we respond to the inability of conventional drugs to simultaneously address both bacterial infection and oxidative stress in the treatment of prostatitis by designing a multifunctional nanoparticle, called QM (Cu) NPs, with dual functionality. QM (Cu) NPs have the capacity to generate reactive oxygen radicals to eradicate bacteria under the influence of laser irradiation. Additionally, they are capable of rapidly scavenging the surplus free radicals, thereby restoring the intracellular redox homeostasis in the absence of laser illumination. A comprehensive characterization of QM (Cu) NPs was conducted, followed by an in-depth analysis of their effects on cells. The therapeutic efficacy of QM (Cu) NPs in multimodal treating bacterial prostatitis was then demonstrated. Furthermore, the outcomes of transcriptomic and molecular biology experiments indicated that QM (Cu) NPs markedly regulate the NF-κB p65 and Nrf2-Keap1 signaling pathways, thereby influencing inflammatory and oxidative stress processes. In conclusion, QM (Cu) NPs simultaneously addressed the dual challenges of antibacterial and antioxidant properties, thereby underscoring their potential clinical applications in the treatment of bacterial prostatitis.

{"title":"MXene-loaded multifunctional nanoparticles with on-demand controlled antimicrobial and antioxidant capacity for multi-modal treating bacterial prostatitis","authors":"Kailai Liu , Yanyao Gao , Yuchen Zhang , Yunhe Zheng , Jiangchuan He , Yu Huang , Xi Chen , Ruixiao Li , Qiang Fu , Bin Song , He Wang , Lei Wang , Geng Zhang , Ke Wang","doi":"10.1016/j.biomaterials.2025.123234","DOIUrl":"10.1016/j.biomaterials.2025.123234","url":null,"abstract":"<div><div>Bacterial prostatitis represents a specific form of prostatitis, primarily resulting from bacterial infection and significantly impairing the life quality of patients. In this paper, we respond to the inability of conventional drugs to simultaneously address both bacterial infection and oxidative stress in the treatment of prostatitis by designing a multifunctional nanoparticle, called QM (Cu) NPs, with dual functionality. QM (Cu) NPs have the capacity to generate reactive oxygen radicals to eradicate bacteria under the influence of laser irradiation. Additionally, they are capable of rapidly scavenging the surplus free radicals, thereby restoring the intracellular redox homeostasis in the absence of laser illumination. A comprehensive characterization of QM (Cu) NPs was conducted, followed by an in-depth analysis of their effects on cells. The therapeutic efficacy of QM (Cu) NPs in multimodal treating bacterial prostatitis was then demonstrated. Furthermore, the outcomes of transcriptomic and molecular biology experiments indicated that QM (Cu) NPs markedly regulate the NF-κB p65 and Nrf2-Keap1 signaling pathways, thereby influencing inflammatory and oxidative stress processes. In conclusion, QM (Cu) NPs simultaneously addressed the dual challenges of antibacterial and antioxidant properties, thereby underscoring their potential clinical applications in the treatment of bacterial prostatitis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123234"},"PeriodicalIF":12.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562902","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

Biocompatibility and therapeutic efficacy of crosslinked hydrogel filled 3D-printed nerve conduit for sacral nerve injury repair

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-03 DOI: 10.1016/j.biomaterials.2025.123230

Jiajia Lu , Yongchuan Li , Jiao Cai , Xingwei Jin , Guangxin Chu , Hai Jin , Lei Zhu , Aimin Chen

Neurological system injuries are debilitating conditions that significantly impact patients' quality of life. This study investigated using a polycaprolactone (PCL) nerve conduit loaded with anti-epidermal growth factor receptor (EGFR) hydrogel and neural stem cells (NSCs) for treating sacral nerve injury (SNI) in rats to explore its neural repair effects. The results demonstrate that the combined transplantation therapy using a 3D printed scaffold filled with crosslinked hydrogel and NSCs effectively improves SNI, with the PCL Nerve conduit showing potential promotion of neuronal differentiation. This research outcome provides a novel approach to the treatment of nerve injuries.

引用次数: 0

Kidney-targeting DNA tetrahedral molecular cage synergistically inhibits acute kidney injury by clearing ROS and activating HO-1

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-03 DOI: 10.1016/j.biomaterials.2025.123237

Yu Ren , Yuhang Dong , Zhi Li , Keying Xu , Jiafeng Xu , Xiangyu Li , Mengmeng Zhang , Changlu Xu , Min Yang , Min Lee , Xiaoming Meng , Jie Wang

Acute kidney injury (AKI) is a major cause of mortality in hospitalized patients, yet effective therapeutic interventions remain underdeveloped. To address this critical need, we have employed tetrahedral framework nucleic acid (tFNA) as a carrier to self-assemble a complex incorporating G-quadruplex and hemin (G4/Hemin). This novel formulation exhibits uniform particle size, targeted delivery, and significant therapeutic efficacy for AKI. In a chemotherapy-induced AKI model, G4/Hemin-tFNA preferentially accumulated in the renal tubules, significantly mitigating drug-induced renal tubular injury. In healthy mice, G4/Hemin-tFNA was rapidly cleared from circulation due to efficient renal filtration. Safety evaluations conducted over a continuous 30-day period indicated minimal side effects associated with G4/Hemin-tFNA administration. Mechanistic studies elucidated three primary molecular mechanisms through which G4/Hemin-tFNA exerts its therapeutic effects in AKI: 1) Enhanced Renal Targeting. G4/Hemin-tFNA facilitates effective renal targeting and protection during blood circulation, leading to significant accumulation of drug within the kidneys. 2) Reactive Oxygen Species (ROS) Clearance. The complex exhibits peroxidase-like activity, enabling the rapid clearance of ROS at the site of AKI lesions, thereby inhibiting the oxidative stress progression. 3) Activation of heme oxygenase-1 (HO-1). G4/Hemin-tFNA selectively activates HO-1, enhancing the concentration of anti-inflammatory factors at inflamed sites and promoting an anti-inflammatory microenvironment. Collectively, these findings demonstrate that G4/Hemin-tFNA is a safe and effective therapeutic agent for AKI. By activating HO-1 and clearing ROS, G4/Hemin-tFNA inhibits disease progression, offering a promising approach for the development of future AKI therapies.

{"title":"Kidney-targeting DNA tetrahedral molecular cage synergistically inhibits acute kidney injury by clearing ROS and activating HO-1","authors":"Yu Ren , Yuhang Dong , Zhi Li , Keying Xu , Jiafeng Xu , Xiangyu Li , Mengmeng Zhang , Changlu Xu , Min Yang , Min Lee , Xiaoming Meng , Jie Wang","doi":"10.1016/j.biomaterials.2025.123237","DOIUrl":"10.1016/j.biomaterials.2025.123237","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a major cause of mortality in hospitalized patients, yet effective therapeutic interventions remain underdeveloped. To address this critical need, we have employed tetrahedral framework nucleic acid (tFNA) as a carrier to self-assemble a complex incorporating G-quadruplex and hemin (G4/Hemin). This novel formulation exhibits uniform particle size, targeted delivery, and significant therapeutic efficacy for AKI. In a chemotherapy-induced AKI model, G4/Hemin-tFNA preferentially accumulated in the renal tubules, significantly mitigating drug-induced renal tubular injury. In healthy mice, G4/Hemin-tFNA was rapidly cleared from circulation due to efficient renal filtration. Safety evaluations conducted over a continuous 30-day period indicated minimal side effects associated with G4/Hemin-tFNA administration. Mechanistic studies elucidated three primary molecular mechanisms through which G4/Hemin-tFNA exerts its therapeutic effects in AKI: 1) Enhanced Renal Targeting. G4/Hemin-tFNA facilitates effective renal targeting and protection during blood circulation, leading to significant accumulation of drug within the kidneys. 2) Reactive Oxygen Species (ROS) Clearance. The complex exhibits peroxidase-like activity, enabling the rapid clearance of ROS at the site of AKI lesions, thereby inhibiting the oxidative stress progression. 3) Activation of heme oxygenase-1 (HO-1). G4/Hemin-tFNA selectively activates HO-1, enhancing the concentration of anti-inflammatory factors at inflamed sites and promoting an anti-inflammatory microenvironment. Collectively, these findings demonstrate that G4/Hemin-tFNA is a safe and effective therapeutic agent for AKI. By activating HO-1 and clearing ROS, G4/Hemin-tFNA inhibits disease progression, offering a promising approach for the development of future AKI therapies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123237"},"PeriodicalIF":12.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550615","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

Mucus-penetrating nanomotor system strengthens mucosal immune response to in situ bacterial vaccine against severe bacterial pneumonia

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-03 DOI: 10.1016/j.biomaterials.2025.123236

Ting Song , Nan Li , Qinhua Zuo , Linghong Huang , Zonghua Liu , Zhong Guo

Pathogens causing major infectious diseases primarily invade through mucosal tissues. Promptly killing these pathogens at the mucosal site and constructing mucosal vaccines in situ can prevent further infections and induce robust mucosal immune responses and memory to prevent reinfection. In this study, we utilized chemotherapy, sonodynamic therapy, and gas therapy to eliminate Streptococcus pneumoniae (S. pneumoniae) colonizing the nasal mucosa. Simultaneously, an in situ pneumococcal vaccine was constructed to elicit specific immune responses and memory. Poly-l-arginine (PArg)-modified ZIF-8 metal-organic frameworks (MOFs) loaded with the ultrasonic sensitizer protoporphyrin IX (PpIX) killed S. pneumoniae in the nasal cavity by multiple mechanisms in the presence of ultrasound. When stimulated by ultrasound, PpIX not only generates reactive oxygen species (ROS) for antimicrobial effect, but these ROS also catalyze the release of nitric oxide (NO) from PArg. NO exerts a motor-like effect that facilitates more efficient passage of nanoparticles through the mucus layer of the alveoli. The immunogenic bacterial debris formed a vaccine formulation by complexing with PArg, which adhered electrostatically to the mucosal surface, facilitating in situ vaccination and inducing mucosal immune responses and memory. This cascade-based combination therapy enabled rapid bacterial eradication and long-term immune prevention. It shortens the traditional vaccine development process, eliminates the spatial distance from pathogen invasion to vaccine development, significantly cuts costs, and addresses vaccine failure due to pathogen mutations. This approach offers a groundbreaking strategy for mucosal vaccine development and the prevention of major infectious diseases.

{"title":"Mucus-penetrating nanomotor system strengthens mucosal immune response to in situ bacterial vaccine against severe bacterial pneumonia","authors":"Ting Song , Nan Li , Qinhua Zuo , Linghong Huang , Zonghua Liu , Zhong Guo","doi":"10.1016/j.biomaterials.2025.123236","DOIUrl":"10.1016/j.biomaterials.2025.123236","url":null,"abstract":"<div><div>Pathogens causing major infectious diseases primarily invade through mucosal tissues. Promptly killing these pathogens at the mucosal site and constructing mucosal vaccines in situ can prevent further infections and induce robust mucosal immune responses and memory to prevent reinfection. In this study, we utilized chemotherapy, sonodynamic therapy, and gas therapy to eliminate <em>Streptococcus pneumoniae</em> (<em>S. pneumoniae</em>) colonizing the nasal mucosa. Simultaneously, an in situ pneumococcal vaccine was constructed to elicit specific immune responses and memory. Poly-<span>l</span>-arginine (PArg)-modified ZIF-8 metal-organic frameworks (MOFs) loaded with the ultrasonic sensitizer protoporphyrin IX (PpIX) killed <em>S. pneumoniae</em> in the nasal cavity by multiple mechanisms in the presence of ultrasound. When stimulated by ultrasound, PpIX not only generates reactive oxygen species (ROS) for antimicrobial effect, but these ROS also catalyze the release of nitric oxide (NO) from PArg. NO exerts a motor-like effect that facilitates more efficient passage of nanoparticles through the mucus layer of the alveoli. The immunogenic bacterial debris formed a vaccine formulation by complexing with PArg, which adhered electrostatically to the mucosal surface, facilitating in situ vaccination and inducing mucosal immune responses and memory. This cascade-based combination therapy enabled rapid bacterial eradication and long-term immune prevention. It shortens the traditional vaccine development process, eliminates the spatial distance from pathogen invasion to vaccine development, significantly cuts costs, and addresses vaccine failure due to pathogen mutations. This approach offers a groundbreaking strategy for mucosal vaccine development and the prevention of major infectious diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123236"},"PeriodicalIF":12.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549445","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