Acta Biomaterialia最新文献

{"title":"A waviness-centered damage model for collagenous soft tissues","authors":"Jia Lu ,&nbsp;Xuehuan He ,&nbsp;Ferdinando Auricchio","doi":"10.1016/j.actbio.2025.01.031","DOIUrl":"10.1016/j.actbio.2025.01.031","url":null,"abstract":"<div><div>This article presents a damage model for collagenous tissue under monotonic loading. Given that the true stretch of collagen fibers is not uniform and is regulated by fiber waviness, we postulate that damage commences from more stretched (i.e. straighter) fibers and progresses to less stretched (i.e. wavier) ones. The complicated nonlinear response is regarded as the outcome of two competing mechanisms: the recruitment of wavy intact fibers and the loss of taut functioning fibers. The progression of damage is modeled by an evolving damage front in the waviness domain. A power law is proposed for the evolution of damage front. The model was fitted to four groups of published uniaxial and biaxial tests data of vascular tissues. Spot-on fits were observed in all groups.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 134-143"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472722","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":"Bidirectional amplification of oxidative stress through the mitochondria-targeted Co-Delivery of nanogolds and chlorin e6 Using ROS-responsive organosilica nanocarriers","authors":"Dongsheng Yu ,&nbsp;Jianming Yuan ,&nbsp;Chiyi Ou ,&nbsp;Qinghua Chen ,&nbsp;Haowen Li ,&nbsp;Chenhui Hao ,&nbsp;Jiaojiao Zheng ,&nbsp;Shuang Liu ,&nbsp;Mingqiang Li ,&nbsp;Du Cheng","doi":"10.1016/j.actbio.2025.01.051","DOIUrl":"10.1016/j.actbio.2025.01.051","url":null,"abstract":"<div><div>Bidirectional amplification of oxidative stress within the mitochondria is essential to enhance photodynamic therapy (PDT), and efficient co-delivery of reducing agents and reactive oxygen species (ROS)-generating agents is critical for achieving this with minimal side effects. However, the absence of an effective platform for mitochondria-targeted co-delivery and spatially controlled tumor-specific therapy limits the potential applicability of this strategy. In this study, we developed an ROS-sensitive organosilica nanocarrier, encapsulating nanogold and introducing chlorin e6 (Ce6) and triphenylphosphine (TPP) through a one-pot sol-gel process. Following TPP-mediated mitochondria-targeted delivery, ROS generated by Ce6 under near-infrared (NIR) irradiation not only damaged the mitochondria but also disrupted the nanoparticles within the tumor, leading to the release of nanogold. These ultra-small nanogolds, due to their high surface area, exhibited enhanced glutathione scavenging capacity, which, in combination with ROS, synergistically amplified oxidative stress to overcome the high resistance of tumor cells. Both in vitro and in vivo experiments confirmed the effectiveness of this strategy, demonstrating efficient co-delivery, controlled drug release, spatially targeted oxidative stress amplification, and synergistic antitumor effects. Thus, we present a facile platform for the spatially controlled bidirectional amplification of oxidative stress with minimal side effects.</div></div><div><h3>Statement of Significance</h3><div>Mitochondrial oxidative stress involves both ROS generation and GSH depletion, indicating that bidirectional amplification is required for mitochondria-targeted antitumor therapy. However, most of existing strategies just focus on ROS generation, which limits the amplification level of oxidative stress. Thus, the mitochondria-targeted co-delivery of photodynamic agent and GSH scavenging agent is an effective approach to address this limitation. Besides, the lack of facile nanoplatform also hinders the application of strategies aimed at bidirectionally amplifying oxidative stress. In this study, we developed a facile nanoplatform for mitochondria-targeted co-delivery of the photodynamic agent Chlorin e6 and GSH scavenging agent nanogold using a ROS-responsive organosilica nanocarrier. This approach successfully achieved bidirectional amplification of oxidative stress, resulting in a synergistic antitumor effect with minimal side effects.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 309-320"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124178","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":"Dual-targeting Aggregation-induced emission polymer micelles mediate immunogenic sonodynamic therapy for Tumor cell growth inhibition and macrophage reprogramming","authors":"Haiheng Peng ,&nbsp;Dandan Wang ,&nbsp;Shiwen Huang ,&nbsp;Aixi Yu","doi":"10.1016/j.actbio.2025.01.065","DOIUrl":"10.1016/j.actbio.2025.01.065","url":null,"abstract":"<div><div>Sonodynamic therapy (SDT) is a promising cancer treatment known for its deep tumor penetration and high efficacy. However, developing highly efficient sonosensitizers remains a significant challenge. Reports on SDT using aggregation-induced emission luminogens (AIEgens) are rare, highlighting the urgent need for novel AIE-active sonosensitizers. For the first time, we have developed tumor- and macrophage-targeting nano micelles, AIE/Biotin/Mannose-M (ABM-M), utilizing aggregation-induced emission polymers. The ABM-M mediate immunogenic cell death through SDT. By reprogramming tumor-associated macrophages (TAMs), they promote the conversion of M2 macrophages into M1 macrophages, reversing the tumor's immunosuppressive environment. We optimized the ratio of functional molecules to achieve maximum fluorescence intensity and reactive oxygen species (ROS) generation. The multi-targeting nature of ABM-M enables them to bind to relevant antibodies or other molecules, enhancing the capture and presentation of tumor antigens. This, in turn, activates the immune responses of dendritic cells and T cells while inhibiting angiogenesis, creating a more favorable microenvironment for antitumor therapy. Furthermore, ABM-M can be combined with immune checkpoint inhibitors, such as anti-PD-L1 antibodies, to achieve promising outcomes in cancer immunotherapy. The ABM-M nanomaterials offer multi-layered and multi-targeting immune regulation. This study provides a blueprint for developing next-generation cancer diagnostic and therapeutic strategies.</div></div><div><h3>Statement of significance</h3><div>Our research pioneers the use of nanomicelles to simultaneously target both tumor cells and tumor-associated macrophages (TAMs), integrated with sonodynamic therapy. Through precise ratio adjustments, we engineered nanomicelles capable of multi-target regulation. These micelles uniquely induce immunogenic cell death (ICD) and repolarize macrophages from an immunosuppressive M2 phenotype to an immunostimulatory M1 phenotype, reversing the tumor's immunosuppressive microenvironment. This dual mechanism can be enhanced by combining with immune checkpoint inhibitors, such as anti-PD-L1 antibodies, offering a promising strategy to treat refractory cancers. Extensive <em>in vitro</em> and <em>in vivo</em> validation confirms their therapeutic potential, providing a solid foundation for clinical application. This innovative approach shows significant promise for revolutionizing cancer treatment and improving patient outcomes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 321-337"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124199","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":"Cationic liposomes as broad-spectrum antidotes for heparin-based anticoagulants","authors":"Jiarui Du ,&nbsp;Yang Liu ,&nbsp;Zhenzhen Dong ,&nbsp;Yubiao Huang ,&nbsp;Yang An ,&nbsp;Xiaoyu Cheng ,&nbsp;Ge Sun ,&nbsp;Chong Du ,&nbsp;Guangjun Nie ,&nbsp;Xueqin Hou ,&nbsp;Yinlong Zhang","doi":"10.1016/j.actbio.2025.02.037","DOIUrl":"10.1016/j.actbio.2025.02.037","url":null,"abstract":"<div><div>Heparin-based anticoagulants have been widely used for the prevention and treatment of venous thrombotic diseases, as well as for anticoagulation during cardiopulmonary bypass and hemodialysis. However, excessive heparin usage brings serious bleeding risk, necessitating immediate reversal of their anticoagulant activity. Additionally, to prevent bleeding during surgery and restore hemostatic function post-cardiopulmonary bypass and hemodialysis, it is also crucial to reverse heparin's anticoagulant effects. Currently, protamine sulfate (PS) is the only clinically approved antidote for heparin. However, its effectiveness against low molecular weight heparin (LMWH) and fondaparinux sodium is limited. Moreover, PS has great potential to trigger fatal allergic reactions. Despite these concerns, no successful clinical substitutes for PS have been developed. In the current work, drawing inspiration from the mechanism by which PS efficiently reverses heparin, we modified the cationic liposome with cationic amino acids, arginine and lysine, to serve as a broad-spectrum antidote (CRKRK-Lipo) for heparin-based anticoagulants. This modification not only enhances their reversal efficiency but also reduces the overall surface charge, potentially improving their biocompatibility. In the tail bleeding and liver injury mouse models, CRKRK-Lipo demonstrated reversal efficiency comparable to PS for heparin and superior reversal efficiency for LMWH and fondaparinux sodium. Notably, CRKRK-Lipo exhibited a wider therapeutic dose window and did not exhibit severe cytotoxicity or immunogenicity, in contrast to PS. It is worth noting that cationic liposomes without polypeptide modification also displayed a significant heparin reversal effect. Our findings not only offer a potential alternative for PS but also broaden the application fields of cationic liposome.</div></div><div><h3>Statement of significance</h3><div>This study introduces the cationic liposomes as a novel and effective alternative to protamine sulfate (PS) for the functional reversal of heparin-based anticoagulants. The results reveal that both CRKRK-modified cationic liposomes (CRKRK-Lipo) and unmodified cationic liposomes (Lipo) showed comparable reversal efficiency to PS for UFH and superior reversal efficiency for LMWH and fondaparinux sodium, with a wider therapeutic dose window and reduced toxicity. This work offers an alternative strategy for detoxifying heparin-based anticoagulants and expands the biomedical applications of cationic liposomes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 283-296"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472737","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":"Endotoxin, not DNA, determines the host response and tissue regeneration behavior of acellular biologic scaffolds","authors":"Wenyue Cheng ,&nbsp;Yonggang Huang ,&nbsp;Jing Dai ,&nbsp;Meibiao Zhao ,&nbsp;Yulu Wang ,&nbsp;Neill Turner ,&nbsp;Jian Zhang","doi":"10.1016/j.actbio.2025.02.010","DOIUrl":"10.1016/j.actbio.2025.02.010","url":null,"abstract":"<div><div>Established quantitative standards for assessing decellularization of biologic scaffolds based on residual DNA levels have been well-documented and widely acknowledged. However, post-implantation complications, such as fever and seroma, are commonly observed which negatively impact clinical outcomes. The presence of cellular debris following decellularization or using source tissues that are naturally high in endotoxin may contribute to the host response to a biologic scaffold. In the study, several multi-step decellularization methods were used to decellularize small intestinal submucosa (SIS) to obtain materials with three distinct levels of residual DNA, lipid residues, and endogenous endotoxin. The potential influence of these residual components on macrophage and lymphocyte polarization <em>in vitro</em>, as well as on the host inflammatory response <em>in vivo</em> post intra-abdominal implantation or abdominal wall defect repair in rats, was assessed. Urinary bladder matrix (UBM) meeting established decellularization criteria and naturally devoid of endotoxin was utilized as a control. The presence of endogenous endotoxin in SIS-ECM resulted in notable changes in macrophage phenotype. SIS-ECM samples with endotoxin levels below FDA limits still upregulated pro-inflammatory factors <em>in vitro</em>. Conversely, SIS with minimal endotoxin content and UBM controls prompted a shift towards a pro-remodeling M2 phenotype, fostering constructive tissue remodeling in a rodent model of abdominal wall defects, irrespective of DNA content. These findings suggest that endotoxin may be a crucial factor influencing biologic scaffolds that are not fully accounted by current decellularization standards.</div></div><div><h3>Statement of significance</h3><div>Clinically utilized decellularized biologic scaffolds that meet the established quantitative standards still suffer problems in high incidence of inflammatory complications, including fever and seroma. In this study, we confirmed that endotoxin, rather than residual DNA, is the crucial factor influencing host responses and regenerative outcomes. Tissue sources and decellularization processes are critical for reducing endotoxin levels and attenuating immuno-inflammatory complications. These findings enhance the evaluation of ECM scaffold performance for clinical application, thereby facilitating improved preparation and utilization for tissue defect repairs.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 157-168"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375108","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":"GSH-responsive Pt-based nanomotor with improved doxorubicin delivery for synergistic osteosarcoma chemotherapy","authors":"Sheng Xu ,&nbsp;Ziwei Hu ,&nbsp;Weihao Zheng ,&nbsp;Chaozhen Qin ,&nbsp;Xiaoyu Bai ,&nbsp;Qinghua Yang ,&nbsp;Tao Zeng ,&nbsp;Dandan Mo ,&nbsp;Bo Zhou ,&nbsp;Chun Lu ,&nbsp;Xiaomin Chen ,&nbsp;Biying Tan ,&nbsp;Jinmin Zhao ,&nbsp;Li Zheng","doi":"10.1016/j.actbio.2025.02.004","DOIUrl":"10.1016/j.actbio.2025.02.004","url":null,"abstract":"<div><div>Osteosarcoma (OS), a highly malignant primary tumor, poses significant threats. Chemotherapy remains the main treatment approach but is limited by low drug bioavailability, poor permeability, and notable side effects. Herein, a near-infrared light (NIR)-driven and GSH-responsive poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP) nanomotor, wherein disulfide bonds served as GSH sponsors and platinum nanoparticles as producers of reactive oxygen species (ROS) to induce cell apoptosis, combined with NIR-driven propulsion to enhance the inhibitory effect of encapsulated doxorubicin (DOX). The results demonstrated that the PSPDP nanomotor can be effectively driven due to its good photothermal properties, with its movement speed increased 2.10 times under NIR laser exposure. Additionally, the efficiency of DOX release increased with the increase in GSH concentration, demonstrating favorable GSH responsiveness. Pt-NPs also exhibited good photothermal properties, enabling self-thermophoresis to drive. Minimal cytotoxic effects of PSPDP were observed on a series of cell lines compared with DOX solution and Pt-NPs. Notably, the Pt-NPs generated a significant amount of ROS, synergistically enhancing the therapeutic effect of DOX, as evidenced by a 5.53-fold increase in OS cell growth inhibition and evident osteosarcoma growth inhibition in the nude mice model. Thus, the NIR-driven, localized, and low-toxic nanomotor may offer a promising therapeutic strategy for OS intervention.</div></div><div><h3>Statement of significance</h3><div>Enhancing drug penetration efficiency and developing delivery systems that respond to the tumor microenvironment to release drugs are effective strategies for treating osteosarcoma (OS). Here, a near-infrared (NIR) light-driven and glutathione (GSH)-responsive nanomotor, integrating poly(ethylene glycol)-SS-polystyrene-doxorubicin and platinum nanoparticles (PSPDP), was produced and used for OS treatment. This PSPDP nanomotor exhibits significant advancements in photothermal activation and self-thermophoresis, enabling a 2.10-fold increase in movement speed under NIR exposure. Such enhanced motility improves the localized delivery and controlled release of doxorubicin, thus increasing drug bioavailability and minimizing systemic toxicity. Additionally, the nanomotor's ability to generate reactive oxygen species significantly amplifies its therapeutic impact, evidenced by a remarkable 5.53-fold increase in tumor growth inhibition. These features make the PSPDP nanomotor a promising candidate for effective and targeted OS treatment strategies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 390-405"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375109","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":"In situ dual-targeted drug delivery system for alleviating imaging and pathological damage in septic arthritis","authors":"Mengxian Wang ,&nbsp;Zeping Yu ,&nbsp;Xinlong Li ,&nbsp;Junqiao Li ,&nbsp;Jianshu Li ,&nbsp;Jun Luo ,&nbsp;Jiyao Li ,&nbsp;Yan Xiong ,&nbsp;Jiaojiao Yang","doi":"10.1016/j.actbio.2025.02.014","DOIUrl":"10.1016/j.actbio.2025.02.014","url":null,"abstract":"<div><div>Septic arthritis is a severe disease that damages articular cartilage and triggers a strong inflammatory response. Current treatments mainly depend on systemic antibiotics and lack effective intra-articular therapies, as well as standardized animal models, and precise detection methods. In this study, we present a drug delivery system responsive to the bacterial microenvironment for targeted inflammation control, along with an effective method for monitoring changes in septic arthritis in SD rats. This system consists a core with pH-sensitive metal-organic frameworks ZIF-8 loading anti-inflammatory drugs indomethacin and a shell with hybrid cell membranes from macrophages (MM) and platelets (PM), refer as MP@ZIF-8@IN. This system, which diverges from traditional treatments, enhances drug utilization, prolongs local retention, and allows for spontaneous release at the treatment site, thereby enabling the exclusive intra-articular treatment of septic arthritis. The drug delivery system inhibits the NF-κB pathway, reduces oxidative stress, and regulates macrophage polarization, preventing cartilage destruction. Additionally, in this standardized animal model utilizing the knee joints of SD rats, we have developed musculoskeletal ultrasound and magnetic resonance imaging for time-based monitoring, thus overcoming the limitation of conventional methods, which are unsuitable for soft tissue analysis. Our findings advance therapeutic strategies for septic arthritis and encourage further application of visualization techniques in related fields.</div></div><div><h3>Statement of significance</h3><div>This study presents significant advancements in the treatment and understanding of septic arthritis. Our customized drug delivery system targets bacteria and macrophages, ensuring long-time drug retention and enhanced inflammation control, all while reducing reliance on antibiotics—an important step toward addressing antibiotic resistance. Additionally, we have refined septic arthritis animal models to establish clearer guidelines for intervention timing, grounded in clinical symptoms and imaging data. This addresses a critical gap in current research and offers a practical framework for future therapeutic approaches.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 363-377"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375110","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":"Proteolysis-targeting chimera-doxorubicin conjugate nanoassemblies for dual treatment of EGFR-TKI sensitive and resistant non-small cell lung cancer","authors":"Junhui Ma ,&nbsp;Ruixue Zhu ,&nbsp;Meijing Li ,&nbsp;Hui Jiao ,&nbsp;Sijun Fan ,&nbsp;Xiang Ma ,&nbsp;Guangya Xiang","doi":"10.1016/j.actbio.2025.02.012","DOIUrl":"10.1016/j.actbio.2025.02.012","url":null,"abstract":"<div><div>Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy for targeted protein degradation and drug discovery. However, traditional PROTACs face inherent limitations and may also contribute to induce drug resistance. These challenges have driven the development of innovative strategies to overcome these obstacles. In current study, a PROTAC-DOX conjugates (PDCs) nanoassembly strategy was introduced to enhance tumor-targeting capability and overcome the drawbacks of conventional PROTACs. The designed PDC-S nanoparticles (PDC-S NPs) demonstrated potent anti-tumor activity against drug-resistant strains (IC₅₀ = 4.7 µM) and improved in vivo efficacy (TGI = 76 %) against drug-sensitive strains, while minimizing side effects. Additionally, PDC-S NPs have great potential in tumor immunotherapy. This study provides a novel and promising strategy for the development of PROTAC-Drug Conjugates (PDCs).</div></div><div><h3>Statement of significance</h3><div>We developed a PROTAC-DOX conjugates (PDCs) nanoassembly strategy to address the limitations of traditional PROTACs, such as poor solubility, low targeting specificity, and drug resistance. PDC-S NPs were constructed via self-assembly, which simplified preparation and minimized the toxicity typically associated with carrier-assisted delivery systems. The PDC-S NPs showed improved aqueous solubility and cellular uptake, resulting in efficient EGFR degradation in HCC827 cells. In vivo, PDC-S NPs accumulated at tumor sites via the EPR effect, resulting in enhanced anti-tumor potency with reduced side effects. Furthermore, PDC-S NPs induced immunogenic cell death (ICD) and suppressed PD-L1 and VEGF expression, highlighting great potential in tumor immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 421-435"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375113","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":"Peroxidase-like copper-doped carbon-dots embedded in hydrogels for stimuli-responsive bacterial biofilm elimination and wound healing","authors":"Lin Li ,&nbsp;Yuhui Wang ,&nbsp;Shixu Hu ,&nbsp;Xiaofan Chang ,&nbsp;Qiaojiao Ding ,&nbsp;Kaizhe Wang ,&nbsp;Yangjun Chen ,&nbsp;Jianping Zheng","doi":"10.1016/j.actbio.2025.02.022","DOIUrl":"10.1016/j.actbio.2025.02.022","url":null,"abstract":"<div><div>Bacterial biofilms and their microenvironment are significant challenges that must be faced in the design of antibacterial drugs. Microenvironment-responsive mimetic peroxidases (POD) have been demonstrated to be an efficient solution to eliminating bacterial biofilms. However, they inevitably require additional H₂O₂ and/or acid due to the poor permeabilities towards biofilms. Herein, we report POD-like copper-doped carbon dots (named CuCD1) synthesized through a facile microwave-assisted carbonization manner. The characteristics of ultrasmall size (&lt; 5 nm) and positive charge enabled it to possess good penetrability toward bacterial biofilm. As expected, CuCD1 showed great damage to bacteria due to the generation of hydroxyl radicals (•OH), which originated from the catalytic decomposition of endogenous H₂O₂ under a weak acid bacterial biofilm microenvironment. This highly increased oxidative stress resulted in the alteration of cell membrane permeability, subsequent cell death, and the final eradication of bacterial biofilm and the exposed bacteria. Moreover, to verify the practicality in vivo, CuCD1 was introduced to a routine hydrogel that was crosslinked by carboxymethyl chitosan (CMCS) and oxidized dextran (ODEX). In comparison with the control groups, the composite hydrogel, i.e., CuCD1-CMCS-ODEX revealed better antibacterial performance and thus accelerated wound healing and collagen disposition. This work would open opportunities to design CDs-based biofilm microenvironment-responsive antibacterial nanoagents.</div></div><div><h3>Statement of significance</h3><div>(1) Ultrasmall size, positively charged, peroxidase (POD)-like CuCD1 were designed and harvested by a facile microwave-assisted carbonization method. (2) CuCD1 revealed a competitive in vitro antibacterial performance, good penetrability, and microenvironment-responsive clearing capacity towards bacterial biofilm. (3) By composing with CMCS-ODEX hydrogel, the composite hydrogel could continuously eliminate bacteria, promote wound healing, as well as collagen disposition. (4) This work would provide a new strategy in the design of CDs-based biofilm microenvironment-responsive antibacterial nano-agents.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 467-478"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412075","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":"Development of a nano-targeting chimera for the degradation of membrane and cytoplasmic proteins","authors":"Peipei Jin ,&nbsp;Zhaozheng Chen ,&nbsp;Ju Zhang ,&nbsp;Haowen Li ,&nbsp;Pengfei Wei ,&nbsp;Ziyu Wang ,&nbsp;Qiyu Feng ,&nbsp;Hongyang Wang ,&nbsp;Da Han ,&nbsp;Yanyan Miao","doi":"10.1016/j.actbio.2025.02.023","DOIUrl":"10.1016/j.actbio.2025.02.023","url":null,"abstract":"<div><div>Various targeted protein degradation (TPD) approaches have been developed to overcome the limitations of traditional drug in eliminating pathogenic proteins by exploiting either the proteasomal or lysosomal pathway. However, there is still a lack of design strategies for TPD that utilize two distinct pathways to achieve the degradation of membrane and cytoplasmic proteins. Here, we develop a Nano-Targeting Chimera (Nano-APTAC), which is engineered by covalently attaching the protein-targeting aptamer to graphene oxide (GO) via the amide linkage, to hijack the autophagy-lysosome and ubiquitin-proteasome systems for targeted degradation of membrane and cytoplasmic proteins respectively. In contrast, a mixture of GO and aptamers without covalent interaction has no effect on protein degradation. Furthermore, the <em>in vivo</em> experiments demonstrate the efficacy of Nano-APTACs in depleting targeted proteins and inhibiting tumor growth. The work provides a versatile programmability platform, employing two distinct degradation systems to facilitate personalized design for the degradation of proteins regardless of their localization on the membrane or cytoplasm, and offering potential therapeutic benefits.</div></div><div><h3>Statement of significance</h3><div>GO and aptamers have been combined for various applications. However, the utilization of this combination in TPD remains unknown. In this study, we found that the Nano-APTAC platform, constructed by covalently linking GO-aptamer chimera (not a simple mixture), can utilize autophagy-lysosome system and ubiquitin-proteasome system to degrade membrane and cytoplasmic proteins, respectively. The types of aptamers significantly influence the intracellular behavior of the chimeras, resulting in distinct subcellular localization and guiding the chimera to select specific degradation systems for protein removal. The Nano-APTAC's mode of action extremely expands the range of targeted proteins, prevents overload in specific degradation systems caused by excessive usage, and provides an exceptional level of adaptability in meeting diverse treatment requirements.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 509-521"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426790","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}