Acta Biomaterialia最新文献

{"title":"Corrigendum to “Injectable, degradable, and mechanically adaptive hydrogel induced by L-serine and allyl-functionalized chitosan with platelet-rich plasma for treating intrauterine adhesions” [Acta Biomaterialia, 2024, 184, 144-155]","authors":"Hongyi Lv , Ruijuan Xu , Xiangyan Xie , Qianqian Liang , Wanting Yuan , Yuting Xia , Xue Ao , Shiqiao Tan , Lijuan Zhao , Jinrong Wu , Yi Wang","doi":"10.1016/j.actbio.2025.02.041","DOIUrl":"10.1016/j.actbio.2025.02.041","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Page 548"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574881","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}

{"title":"Exploration of biomaterial-tissue integration in heterogeneous microporous annealed particle scaffolds in subcutaneous implants over 12 months","authors":"Ethan Nicklow ,&nbsp;Lauren J. Pruett ,&nbsp;Neharika Singh ,&nbsp;James J. Daniero ,&nbsp;Donald R. Griffin","doi":"10.1016/j.actbio.2025.02.020","DOIUrl":"10.1016/j.actbio.2025.02.020","url":null,"abstract":"<div><div>Microporous annealed particle (MAP) scaffolds are comprised of hydrogel microparticles with inter- and intra-particle cross-links that provide structure and cell-scale porosity, making them an increasingly attractive option for injectable tissue augmentation. Many current injectable biomaterials create a substantial foreign body response (FBR), while MAP scaffolds mitigate this response and have the potential to facilitate the formation of new tissue, though this <em>de novo</em> tissue formation is poorly understood. Here, we leverage a subcutaneous implant model to explore the maturation of MAP implants with and without heparin microislands (µislands) over one year to identify the effect of bioactive particles on scaffold maturation. Implants were measured and explanted after 1, 3, 6, and 12 months and analyzed using immunofluorescence staining and RNA-sequencing. No fibrous capsule or significant FBR was observed, and though a significant amount of MAP remains at 12 months, we still see a volume decrease over time. Heparin µislands facilitate increased cell infiltration and recruit a wider variety of cells at 1 month than blank MAP scaffolds, although this effect diminishes after 3 months. Transcriptomics reveal a potential activation of the complement-mediated immune response at 12 months in both groups, possibly associated with pore collapse in the implants. A single 12-month sample avoided this outcome, yielding complete cell infiltration, vascularization, and substantial matrix deposition throughout. Future work will characterize the effect of implantation site and facilitate increased matrix deposition to support the scaffold and prevent pore collapse.</div></div><div><h3>Statement of significance</h3><div>Injectable biomaterials are increasingly used clinically for soft tissue augmentation and regeneration but still face significant issues from the foreign body reaction. While some materials intentionally promote this response to stimulate collagen deposition, porous materials like MAP scaffolds can mitigate the immune response and allow for true tissue integration. However, this integration is poorly understood, particularly on long timescales, as traditional materials are dominated by inflammatory signals. In this work, we leverage a minimally inflammatory subcutaneous implant to investigate the maturation of MAP scaffolds with and without bioactive heparin-containing particles. The results presented here contribute a better understanding of the long-term material-tissue dynamics of MAP scaffolds that can inform future material design for tissue augmentation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 183-197"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434495","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}

{"title":"Mechanosensing alters platelet migration","authors":"Hendrik von Eysmondt,&nbsp;Jan Seifert,&nbsp;Johannes Rheinlaender,&nbsp;Tilman E. Schäffer","doi":"10.1016/j.actbio.2025.02.042","DOIUrl":"10.1016/j.actbio.2025.02.042","url":null,"abstract":"<div><div>Platelets have long been established as a safeguard of our vascular system. Recently, haptotactic platelet migration has been discovered as a part of the immune response. In addition, platelets exhibit mechanosensing properties, changing their behavior in response to the stiffness of the underlying substrate. However, the influence of substrate stiffness on platelet migration behavior remains elusive. Here, we investigated the migration of platelets on fibrinogen-coated polydimethylsiloxane (PDMS) substrates with different stiffnesses. Using phase-contrast and fluorescence microscopy as well as a deep-learning neural network, we tracked single migrating platelets and measured their migration distance and velocity. We found that platelets migrated on stiff PDMS substrates (<em>E</em> = 2 MPa), while they did not migrate on soft PDMS substrates (<em>E</em> = 5 kPa). Platelets migrated also on PDMS substrates with intermediate stiffness (<em>E</em> = 100 kPa), but their velocity and the fraction of migrating platelets were diminished compared to platelets on stiff PDMS substrates. The straightness of platelet migration, however, was not significantly influenced by substrate stiffness. We used scanning ion conductance microscopy (SICM) to image the three-dimensional shape of migrating platelets, finding that platelets on soft substrates did not show the polarization and shape change associated with migration. Furthermore, the fibrinogen density gradient, which is generated by migrating platelets, was reduced for platelets on soft substrates. Our work demonstrates that substrate stiffness, and thus platelet mechanosensing, influences platelet migration. Substrate stiffness for optimal platelet migration is quite high (&gt;100 kPa) in comparison to other cell types, with possible implications on platelet behavior in inflammatory and injured tissue.</div></div><div><h3>Statement of Significance</h3><div>Platelets can feel and react to the stiffness of their surroundings - a process called mechanosensation. Additionally, platelets migrate via substrate-bound fibrinogen as part of the innate immune response during injury or inflammation. It has been shown that the migration of immune cells is influenced by the stiffness of the underlying substrate, but the effect of substrate stiffness on the migration of platelets has not yet been investigated. Using differently stiff substrates made from PDMS, we show that substrate stiffness affects platelet migration. Stiff substrates facilitate fast and frequent platelet migration with a strong platelet shape anisotropy and a strong fibrinogen removal while soft substrates inhibit platelet migration. These findings highlight the influence of the stiffness of the surrounding tissue on the platelet immune response, possibly enhancing platelet migration in inflamed tissue.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 213-221"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476553","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}

{"title":"Ex-vivo mechano-structural characterization of fresh diseased human esophagus","authors":"Nicolas A. Alderete ,&nbsp;Jin W. Hwang ,&nbsp;Meisam Asgari ,&nbsp;Ryan Benavides ,&nbsp;Sourav Halder ,&nbsp;Leyu Sun ,&nbsp;Dustin Carlson ,&nbsp;Eric Goudie ,&nbsp;Domenico A. Farina ,&nbsp;Sam Kim ,&nbsp;Daniel P. Pearce ,&nbsp;Colleen M. Witzenburg ,&nbsp;Neelesh A. Patankar ,&nbsp;Guan-Yu Yang ,&nbsp;John E. Pandolfino ,&nbsp;Sevketcan Sarikaya ,&nbsp;Horacio D. Espinosa","doi":"10.1016/j.actbio.2025.02.051","DOIUrl":"10.1016/j.actbio.2025.02.051","url":null,"abstract":"<div><div>The esophagus, the tube-like organ responsible for transporting food from the pharynx to the stomach, operates as a highly mechanical structure, exhibiting complex contraction and distension patterns triggered by neurological impulses. Despite the critical role of mechanics in its function and the need for high-fidelity models of esophageal transport, mechanical characterization studies of human esophagus remain relatively scarce. In addition to the paucity of studies in human specimens, the available results are often scattered in terms of methodology and scope, making it difficult to compare findings across studies and thereby limiting their use in computational models. In this work, we present a detailed passive-mechanical and structural characterization of the esophageal muscular layers, excised from short esophageal segments obtained from live patients with varied clinical presentations. Specifically, we conducted uniaxial and planar biaxial extension tests on the smooth muscle layers, complemented by pre- and post-testing structural characterization via histological imaging. Unlike existing studies, our experimental results on passive behavior are discussed in the context of physiological relevance (e.g., physiological stretches, and activity-inhibiting pathologies), providing valuable insights that guide the subsequent modeling of the esophagus’ mechanical response. As such, this work provides new insights into the passive properties of the fresh human esophagus, expands the existing database of mechanical parameters for computational modeling, and lays the foundation for future studies on active mechanical properties.</div></div><div><h3>Statement of significance</h3><div>Understanding the mechanical properties of the esophagus is crucial for developing accurate models of its function and suitable replacements. This study provides insights into the passive mechanical behavior of fresh human esophageal tissue, enhancing our understanding of how it responds to stretching under physiological conditions. By characterizing the properties of different esophageal layers, obtained from esophagectomy specimens with various presentations, and considering their relevance to both normal and abnormal functioning, this work addresses the gap in ex-vivo human esophagus studies. The findings emphasize the importance of contextually analyzing experimental results within physiological parameters and suggest avenues for future research to further refine our understanding of esophageal mechanics, paving the way for improved diagnostic and therapeutic approaches in managing esophageal disorders.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 257-270"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532182","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}

{"title":"The interplay between endothelial glycocalyx maturity and both the toxicity and intracellular uptake of charged nanoparticles","authors":"Claire A. Bridges ,&nbsp;Lu Fu ,&nbsp;Jonathan Yeow ,&nbsp;Xiaojing Huang ,&nbsp;Miriam Jackson ,&nbsp;Rhiannon P. Kuchel ,&nbsp;James D. Sterling ,&nbsp;Shenda M. Baker ,&nbsp;Megan S. Lord","doi":"10.1016/j.actbio.2025.03.012","DOIUrl":"10.1016/j.actbio.2025.03.012","url":null,"abstract":"<div><div>Nanoparticles are widely studied for delivering treatments to target tissues, but few have reached clinical use. Most nanoparticles encounter blood vessels on their way to target tissues. The inner surface of these vessels is lined with endothelial cells covered by a glycocalyx, an extracellular matrix rich in anionic glycans. The role of the glycocalyx in nanoparticle interactions is not well understood. Here, we demonstrate that endothelial cells need extended culture times to synthesize a mature glycocalyx. Our research shows that branched polyethyleneimine functionalized gold nanoparticles bind to endothelial cells expressing either a developing or mature glycocalyx, with the interaction involving hyaluronan and heparan sulfate. These nanoparticles are subsequently internalized. Similar results were seen with poly(L-arginine). A mature glycocalyx protects cells by reducing the toxicity of these cationic nanoparticles. In contrast, lipoic acid-functionalized gold nanoparticles are internalized by cells with a developing glycocalyx, but not a mature one. Poly(L-glutamic acid) only interacts with cells when major glycans in the glycocalyx are degraded. These findings highlight the complex relationship between nanoparticle charge and structure, and their effects on toxicity, binding, and uptake by endothelial cells. This offers important insights for improving nanoparticle interactions with blood vessels in health and disease.</div></div><div><h3>Statement of Significance</h3><div>Endothelial cells lining blood vessels form a barrier through which nanoparticles must cross to reach target tissues. These cells are covered with a layer called the glycocalyx, which is rich in anionic glycans. However, the role of the glycocalyx in how nanoparticles interact with cells remains underexplored.</div><div>Our research revealed that cells with a mature glycocalyx internalize cationic nanoparticles and experience reduced cytotoxicity. Conversely, a mature glycocalyx prevents anionic nanoparticles from entering cells. These results suggest that the structure of both the nanoparticles and the glycocalyx should be considered in future studies to improve the use of nanoparticles for medical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 293-306"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588723","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}

{"title":"Impact-absorbing helmet design inspired by walnut texture reaction-diffusion mechanisms","authors":"Nengzhuo Chou ,&nbsp;Sen Lin ,&nbsp;Xu Fang ,&nbsp;Zerong Du ,&nbsp;Jiahan Zhong ,&nbsp;Guangyao Li ,&nbsp;Dingwen Bao ,&nbsp;Guoping Wang ,&nbsp;Yi Min Xie","doi":"10.1016/j.actbio.2025.02.050","DOIUrl":"10.1016/j.actbio.2025.02.050","url":null,"abstract":"<div><div>This study investigates the complex textures on walnut shells, which play a vital role in enhancing crashworthiness performance. Despite the challenges in deciphering their functionality and formation, we discovered that these textures can be described by reaction-diffusion equations. These equations capture the shell hardening mechanism and simulate texture formation based on observed lignin diffusion patterns. The texture sample sets, derived from diverse local sampling positions and scopes, were analyzed using a Convolutional Neural Network classification model to determine the most representative texture classes. The parameter combinations from the control equations, integrated with impact risk assessments and personalized needs, informed the design of a protective helmet. Physical and numerical tests confirmed the helmet's impact-absorption capabilities. These insights pave the way for the development of impact-resistant devices, such as bio-armor and shell for automotive parts.</div></div><div><h3>Statement of significance</h3><div>This study investigates the complex textures on walnut shells, which play a vital role in enhancing crashworthiness performance. We discovered that these textures can be described by reaction-diffusion equations, which capture the shell hardening mechanism and simulate texture formation based on observed lignin diffusion patterns. The texture were analyzed using a Convolutional Neural Network classification model to determine the most representative texture classes. The parameter combinations from the control equations, integrated with impact risk assessments and personalized needs, informed the design of a protective helmet. Physical and numerical tests confirmed the helmet's impact-absorption capabilities. These insights pave the way for the development of impact-resistant devices, such as bio-armor and shell for automotive parts.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 244-256"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532197","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}

{"title":"Oral delivery of ultra-small zwitterionic nanoparticles to overcome mucus and epithelial barriers for macrophage modulation and colitis therapy","authors":"Changshun Zhao ,&nbsp;Suchen Wen ,&nbsp;Rui Xu ,&nbsp;Ke Wang ,&nbsp;Yinan Zhong ,&nbsp;Dechun Huang ,&nbsp;Bingbing Zhao ,&nbsp;Wei Chen","doi":"10.1016/j.actbio.2025.02.039","DOIUrl":"10.1016/j.actbio.2025.02.039","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that poses significant therapeutic challenges due to the intestinal mucus and epithelial barriers. In this study, ultra-small zwitterionic nanoparticles (HC-CB NPs) is developed based on glutathione (GSH)-responsive hyperbranched polycarbonate to enhance the oral delivery of drugs and overcome these physiological barriers. HC-CB NPs demonstrate high colloidal stability across a wide range of pH environments and physiological fluids, preventing premature drug release within the gastrointestinal tract. The ultra-small sized HC-CB NPs demonstrate minimal mucin adsorption and effectively penetrate through the mucus layer, and the zwitterion surface further facilitate epithelial barrier crossing via the proton-assisted amino acid transporter 1 (PAT1) pathway. HC-CB NPs mediate enhanced macrophage uptake via monocarboxylate transporters (MCTs) pathway and ultimately improved therapy efficacy on colitis. The <em>in vivo</em> results reveal that FK506-loaded HC-CB NPs (HC-CB NPs@FK506) significantly reduce inflammatory markers (TNF-α, IL-6) and myeloperoxidase (MPO) levels, while promoting epithelial integrity by increasing E-cadherin expression. This study offers a promising approach to overcoming intestinal barriers in oral UC treatment, offering biocompatibility and potential for clinical translation.</div></div><div><h3>Statement of significance</h3><div>Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that poses significant therapeutic challenges due to the intestinal mucus and epithelial barriers. This study explores an oral UC therapy using ultra-small zwitterionic nanoparticles (HC-CB NPs) constructed from GSH-responsive hyperbranched polycarbonate. Compared to existing strategies, HC-CB NPs demonstrate minimal mucin adsorption and effectively penetrate through the mucus layer, and the zwitterion surface further facilitate epithelial barrier crossing via the proton-assisted amino acid transporter 1 (PAT1) pathway. Additionally, HC-CB NPs mediate enhanced macrophage uptake via monocarboxylate transporters (MCTs) pathway, resulting in improved therapeutic efficacy. These findings underscore the potential of HC-CB NPs as a transformative platform for overcoming intestinal barriers in UC treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 399-409"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472994","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}

{"title":"Spatially targeted triple amplification of oxidative stress for enhanced tumor therapy via effective modulation of metal ion valence states","authors":"Jing Yu ,&nbsp;Chen Wang ,&nbsp;Fan Zhao,&nbsp;Zhengtao Xu,&nbsp;Yuxin Zhang,&nbsp;Yao Ying,&nbsp;Wangchang Li,&nbsp;Juan Li,&nbsp;Jingwu Zheng,&nbsp;Liang Qiao,&nbsp;Shenglei Che","doi":"10.1016/j.actbio.2025.02.038","DOIUrl":"10.1016/j.actbio.2025.02.038","url":null,"abstract":"<div><div>Inducing oxidative stress through metal ions activated biocatalysis is a fundamental mechanism of metal ion-interference therapy (MIIT). However, the actual catalytic efficiency of MIIT is often limited by the random valence states of metal ions and scattered space. Herein, copper-iron bimetallic sulfide nanoparticles coated with bovine serum albumin (CFS NPs) are synthesized through metal ion valence modulation strategy. Significant amounts of Cu⁺ and Fe²⁺ were released by CFS NPs, which is crucial for catalyzing Fenton-like reaction. The presence of Fe³⁺ further boosts Fe²⁺ availability and protects against hydroxyl radical (•OH) elimination via glutathione (GSH) consumption, amplifying the mitochondrial oxidative stress to induce apoptotic cell death. This oxidative stress damage is manifested in Cu⁺ targeting the mitochondrial tricarboxylic acid (TCA) cycle, further causing proteotoxic stress and cuproptosis. The production of lipid peroxidation (LPO) and the inactivation of glutathione peroxidase 4 (GPX4) expression are also affected by the amplified oxidative stress to achieve efficient ferroptosis. As a result, the synergistic apoptosis/cuproptosis/ferroptosis multimodal therapy almost completely inhibits tumor growth in vivo. It is believing that CFS NPs provide feasible implications for multiple combination therapy of tumors with the rational regulation of metal ion valence state and precise spatial control to effectively improve the level of oxidative stress.</div></div><div><h3>Statement of Significance</h3><div><strong>:</strong> Metal ion-interference therapy induces oxidative stress in tumor cells via metal ion-activated biocatalysis, influencing reactive oxygen species (ROS) levels, proteotoxic stress, and lipid peroxidation accumulation. However, the actual catalytic efficiency of metal ion-interference therapy is often limited by the random valence state of these metal ions and scattered space. Herein, we constructed variable valence copper-iron bimetallic sulfides nanoparticles (CFS NPs) through metal ion valence modulation strategy to overcome the key factors that constrain efficiency with the combination of triple oxidative stress spatially treatment for apoptosis/cuproptosis/ferroptosis therapy. The reduced acidity and GSH concentration within normal cells lead to a much low cytotoxicity to normal cells, and therefore higher biocompatibility and biosafety for bio-medical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 321-331"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473219","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}

{"title":"DNA nanovaccines derived from ferritin-modified glycogens for targeted delivery to immature dendritic cells and for promotion of Th1 cell differentiation","authors":"Jun Wu ,&nbsp;Jing Liang ,&nbsp;Sichen Li ,&nbsp;Jinjin Lu ,&nbsp;Juan Zhou ,&nbsp;Min Gao ,&nbsp;Yan Zhang ,&nbsp;Jinghua Chen","doi":"10.1016/j.actbio.2025.02.057","DOIUrl":"10.1016/j.actbio.2025.02.057","url":null,"abstract":"<div><div>DNA vaccines have emerged as a powerful approach for advanced cancer therapy. Despite the development of various delivery systems to enhance the immunogenicity of DNA vaccines, many still face challenges such as limited DNA condensation, rapid degradation <em>in vivo</em> and insufficient targeting to lymph nodes (LNs). Synthetic dendrimers with modifiable surfaces exhibit high efficiency in DNA condensation, but their synthesis is extremely complex. This study utilizes cationic glycogen, a natural branched dendrimer-like polymer, as the core structure for efficient DNA condensation and delivery, ensuring good biocompatibility. By connecting ferritin light chain to the glycogen surfaces, active targeting of LNs can be achieved due to its affinity for the SCARA5 receptor on immature dendritic cells (DCs), facilitating vaccine migration to the LNs. In addition, a seperate plasmid encoding adjuvant IL-12 was co-delivered to further boost the immunogenicity of the DNA nanovaccine. <em>In vivo</em> and <em>in vitro</em> experiments confirmed the effective transfection capability of this DNA vaccine, demonstrating promoted DC maturation, increased antigen presentation, and Th1 cell differentiation, resulting in improved anti-tumor efficiency <em>in vivo</em>. This innovative multi-gene co-loaded DNA vaccine offers valuable insights into combined gene therapy and broadens the research horizon on non-viral gene carriers.</div></div><div><h3>Statement of Significance</h3><div>The DNA vaccine encounters challenges such as limited DNA condensation, rapid degradation and insufficient targeting to lymph nodes (LNs), resulting in generally weak immunogenicity. In the current study, a novel nanovaccine is developed by connecting ferritin light chain to natural dendrimer glycogen, for simultaneous delivery of dual plasmids. The cationized glycogen provides strong DNA condensation ability, while ensuring excellent stability of the nanovaccine. The presence of ferritin light chain leads to effective targeting of dendritic cells (DCs), facilitating its migration to LNs. Moreover, the plasmid encoding the adjuvant IL-12 is co-incorporated with the antigen plasmid to mitigate the immunosuppression environment. This strategy significantly improves the immunogenicity of DNA vaccines, demonstrating high efficiency in cancer immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 436-452"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538222","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}

{"title":"Arsenene-Vanadene nanodots co-activate Apoptosis/Ferroptosis for enhanced chemo-immunotherapy","authors":"Li He ,&nbsp;WeiYe Ren ,&nbsp;WeiYi Cheng ,&nbsp;JingQuan Chen ,&nbsp;Jianjun Lai ,&nbsp;Yajun Wu ,&nbsp;Zhibing Wu ,&nbsp;Dandan Bao ,&nbsp;Yinghui Wei ,&nbsp;Ji-Gang Piao","doi":"10.1016/j.actbio.2025.02.059","DOIUrl":"10.1016/j.actbio.2025.02.059","url":null,"abstract":"<div><div>Triple-Negative Breast Cancer (TNBC) represents a highly aggressive subtype of breast cancer with an unfavorable prognosis, characterized by minimal immune infiltration and pronounced immune suppression, resulting in a limited response to immunotherapy. In this study, a multifunctional Arsenene-Vanadene nanodot (AsV) drug delivery system is introduced, which responds to the tumor microenvironment by releasing arsenic and vanadium. Arsenic undergoes oxidation to generate highly toxic trivalent arsenic, which induces apoptosis in tumor cells while utilizing apoptotic cell debris to transiently activate the immune system. Additionally, arsenic binds to cysteine, indirectly facilitating ferroptosis. Concurrently, vanadium's redox cycling properties are harnessed to trigger a Fenton-like reaction, promoting lipid peroxidation. Furthermore, ferroptosis is enhanced through the depletion of glutathione and inactivation of glutathione peroxidase 4 (GPX4), leading to the release of damage-associated molecular patterns and thereby amplifying the anti-tumor immune response. This study represents the first instance of integrating arsenene's apoptosis-inducing properties with vanadium's ferroptosis-enhancing effects, providing a synergistic approach to improving the immunotherapeutic response and offering a potential strategy for enhancing TNBC prognosis.</div></div><div><h3>Statement of Significance</h3><div>Triple-negative breast cancer (TNBC) exhibits resistance to immunotherapy due to its highly immunosuppressive tumor microenvironment. In this study, tumour-responsive Arsenene-Vanadene nanodots (AsV) were developed to induce a synergistic effect by triggering apoptosis and ferroptosis through microenvironment-specific mechanisms. The arsenic component generates cytotoxic trivalent arsenic, promoting apoptosis while binding to cysteine, thereby reducing GSH synthesis. Simultaneously, vanadium initiates lipid peroxidation through Fenton-like reactions and disruption of the glutathione/GPX4 axis, further amplifying ferroptotic cell death. This dual-action system transforms tumor cell debris into immune-stimulating signals while circumventing conventional immunotherapy limitations. As the first strategy integrating arsenic-induced apoptosis with vanadium-enhanced ferroptosis, this approach provides a mechanistic framework to overcome TNBC immunosuppression through coordinated cell death pathways, demonstrating potential for precision nanomedicine applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 453-470"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544939","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}