Acta Biomaterialia最新文献

{"title":"Assembly of a biomimetic copper-based nanocomplex for alleviating hypoxia to enhance cuproptosis against osteosarcoma and lung metastasis","authors":"Junyong Wu ,&nbsp;Xinyan Hao ,&nbsp;Lin Qi ,&nbsp;Wenjie Xu ,&nbsp;Chi Yin ,&nbsp;Yucheng Tang ,&nbsp;Pengcheng Sun ,&nbsp;Dehua Liao ,&nbsp;Xiongbin Hu ,&nbsp;Tiantian Tang ,&nbsp;Chao Tu ,&nbsp;Daxiong Xiang ,&nbsp;Zhihong Li","doi":"10.1016/j.actbio.2024.12.049","DOIUrl":"10.1016/j.actbio.2024.12.049","url":null,"abstract":"<div><div>Osteosarcoma tissues demonstrated elevated expression of proteins (FDX1 and DLAT) integral to cuproptosis in our preliminary study, indicating the potential effectiveness of anti-tumor strategies predicated on this process. Nevertheless, the overexpression of copper export proteins and the challenge of copper ion penetration may contribute to insufficient local copper ion concentration for inducing cuproptosis. Herein, we engineered a biomimetic copper-elesclomol-polyphenol network for the efficient delivery of copper ions and the copper ionophore elesclomol. Simultaneously, we integrated catalase (CAT) to alleviate tumor hypoxia, thereby inducing a greater reliance of tumor cells on aerobic respiration and enhancing cuproptosis sensitivity. In vitro analyses revealed that the nanocomplex exhibited potent cytotoxicity and displayed hallmark characteristics of cuproptosis. In vivo trials further validated targeted tumor accumulation, resulting in the suppression of tumor growth and lung metastasis. An augmentation in the proportion of activated immune cells in both tumor and draining lymph nodes was observed. The improvement of immunosuppressive microenvironment facilitated a synergistic antitumor effect with cuproptosis. The therapeutic efficacy was further evidenced in two osteosarcoma models, highlighting the potential as a safe and effective strategy against osteosarcoma and lung metastasis.</div></div><div><h3>Statement of significance</h3><div>Osteosarcoma tissues exhibit a marked increase in the expression of proteins FDX1 and DLAT, which are crucial for cuproptosis. Moreover, cells that depend on mitochondrial respiration are more susceptible to cuproptosis. Here we developed a biomimetic copper-based nanocomplex to trigger cuproptosis against osteosarcoma and lung metastases. The nanocomplex demonstrated excellent biocompatibility and tumor targeting. Catalase incorporating facilitated oxygen generation within tumor microenvironment and alleviated hypoxia, thereby inducing a greater reliance of tumor cells on aerobic respiration and enhancing cuproptosis sensitivity. Simultaneously, the released Cu-elesclomol complexes induced proteotoxic stress responses and efficiently elicited cuproptosis, leading to increased release of proinflammatory factors and triggering anti-tumor immune activation. Our strategy holds promise for osteosarcoma treatment by inducing cuproptosis and achieving potent tumor suppression.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 348-361"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878929","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":"Impact of nanoparticle properties on immune cell interactions in the lymph node","authors":"Muhammad Asim Farooq,&nbsp;Angus P.R. Johnston,&nbsp;Natalie L. Trevaskis","doi":"10.1016/j.actbio.2024.12.039","DOIUrl":"10.1016/j.actbio.2024.12.039","url":null,"abstract":"<div><div>The lymphatic system plays an important role in health and many diseases, such as cancer, autoimmune, cardiovascular, metabolic, hepatic, viral, and other infectious diseases. The lymphatic system is, therefore, an important treatment target site for a range of diseases. Lymph nodes (LNs), rich in T cells, B cells, dendritic cells, and macrophages, are also primary sites of action for vaccines and immunotherapies. Promoting the delivery of therapeutics and vaccines to LNs can, therefore, enhance treatment efficacy and facilitate avoidance of off-target side effects by enabling a reduction in therapeutic dose. Several nanoparticle (NP) based delivery systems, such as polymeric NPs, lipid NPs, liposomes, micelles, and dendrimers, have been reported to enhance the delivery of therapeutics and/or vaccines to LNs. Specific uptake into the lymph following injection into tissues is highly dependent on particle properties, particularly particle size, as small molecules are more likely to be taken up by blood capillaries due to higher blood flow rates, whereas larger molecules and NPs can be specifically transported via the lymphatic vessels to LNs as the initial lymphatic capillaries are more permeable than blood capillaries. Once NPs enter LNs, particle properties also have an important influence on their disposition within the node and association with immune cells, which has significant implications for the design of vaccines and immunotherapies. This review article focuses on the impact of NP properties, such as size, surface charge and modification, and route of administration, on lymphatic uptake, retention, and interactions with immune cells in LNs. We suggest that optimizing all these factors can enhance the efficacy of vaccines or therapeutics with targets in the lymphatics and also be helpful for the rational design of vaccines.</div></div><div><h3>Statement of Significance</h3><div>The lymphatic system plays an essential role in health and is an important treatment target site for a range of diseases. Promoting the delivery of immunotherapies and vaccines to immune cells in lymph nodes can enhance efficacy and facilitate avoidance of off-target side effects by enabling a reduction in therapeutic dose. One of the major approaches used to deliver therapeutics and vaccines to lymph nodes is via injection in nanoparticle delivery systems. This review aims to provide an overview of the impact of nanoparticle properties, such as size, surface charge, modification, and route of administration, on lymphatic uptake, lymph node retention, and interactions with immune cells in lymph nodes. This will inform the design of future improved nanoparticle systems for vaccines and immunotherapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 65-82"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866572","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":"Corrigendum to “Shape-Fixing Hydrogel Promotes Scarless Healing of a Wound Under Tension” [Acta Biomaterialia, 183, 2024, 173-190]","authors":"Danlan Fu ,&nbsp;Junfei Huang ,&nbsp;Xiaoqi Wu ,&nbsp;Yue Li ,&nbsp;Yufan Zhang ,&nbsp;Lu Chen ,&nbsp;Zhen Liu ,&nbsp;Ye He ,&nbsp;Yi Zhou ,&nbsp;Lunan Yang ,&nbsp;Zhiqi Hu ,&nbsp;Yong Miao","doi":"10.1016/j.actbio.2024.12.054","DOIUrl":"10.1016/j.actbio.2024.12.054","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 639-640"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933886","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":"A prodrug nanodevice co-delivering docetaxel and ROR1 siRNA for enhanced triple negative breast cancer therapy","authors":"Lixuan Yin ,&nbsp;Zirang Fu ,&nbsp;Mengmeng Wang ,&nbsp;Bo Liu ,&nbsp;Xujie Sun ,&nbsp;Kaiyue Liu ,&nbsp;Xiaolong Feng ,&nbsp;Zongyan He ,&nbsp;Yutong Wang ,&nbsp;Jiazhen Hou ,&nbsp;Xinyue Shao ,&nbsp;Ning Yang ,&nbsp;Tian Zhang ,&nbsp;Yiran Liu ,&nbsp;Zhengwei Huang ,&nbsp;Qi Yin ,&nbsp;Yuanchao Xie ,&nbsp;Yaping Li ,&nbsp;Tianqun Lang","doi":"10.1016/j.actbio.2024.12.055","DOIUrl":"10.1016/j.actbio.2024.12.055","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) has been a clinical challenge due to its high recurrence and metastasis rates. Chemotherapy remains the primary treatment for TNBC after surgery ablation, but it lacks targeted specificity and causes side effects in normal tissues. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is significantly expressed in TNBC cells, and small interference RNA (siRNA) targeting ROR1 can effectively suppress ROR1 gene expression, thereby inhibiting proliferation and metastasis. However, clinical application of ROR1 siRNA is limited by susceptibility to clearance and difficulty in endosomal escape. In this study, the docetaxel (DTX) prodrug nanoparticle BBRM delivering ROR1 siRNA was constructed. The BBRM could be effectively internalized by tumor cells and endosomal escape to release DTX and ROR1 siRNA. In 4T1 tumor-bearing mice, BBRM could be targeting delivered to tumor and lung tissues, with good biosafety, achieving a tumor inhibition rate of 74.1 % and inhibiting lung metastasis. By integrating chemotherapy and RNA interference therapy, BBRM successfully co-delivered chemotherapeutic agents and siRNA to improve the therapeutic efficacy of triple-negative breast cancer and provided a promising strategy for clinical transformation.</div></div><div><h3>Statement of significance</h3><div>Chemotherapy is still the primary treatment for triple-negative breast cancer (TNBC) after surgery ablation, but it causes side effects without targeting capacity. ROR1 is significantly expressed in TNBC cells, and RNA interference for ROR1 can suppress ROR1 gene expression to inhibit tumor proliferation. However, as oligonucleotides, effect of ROR1 siRNA is limited by susceptibility to clearance and difficulty in endosomal escape. In this work, we designed a nanodevice based on a docetaxel (DTX) prodrug that targets ROR1 for the synergistic therapy of TNBC. We constructed a nanoparticle (BBRM) for co-delivery of the DTX and ROR1 siRNA. The BBRM could be effectively internalized by tumor cells and endosomal escape. The ROR1 siRNA downregulated ROR1 protein expression and improved the anti-proliferative and anti-metastatic effects. In addition, BBRM reversed the immunosuppressive tumor microenvironment, thus improving breast cancer therapeutic efficacy. It was a pioneering investigation in synergistic chemo-gene therapy by co-delivering DTX and ROR1 siRNA for TNBC treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 498-513"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901057","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 oxygen-supplying ROS nanopurifier for enhanced healing of MRSA-infected diabetic wounds via microenvironment modulation","authors":"Qi Wang ,&nbsp;Zheng Luo ,&nbsp;Zhiguo Li ,&nbsp;Haohua Hu ,&nbsp;Yuting Lin ,&nbsp;Xiaotong Fan ,&nbsp;Zibiao Li ,&nbsp;Yun-Long Wu","doi":"10.1016/j.actbio.2024.12.044","DOIUrl":"10.1016/j.actbio.2024.12.044","url":null,"abstract":"<div><div>Hypoxia, high ROS levels and chronic inflammation are the main factors that hinder the healing of diabetic wounds. Long-term exposed wounds are prone to bacterial infection, especially MRSA infection, which exacerbates the complex wound microenvironment of diabetes and threatens patients’ lives. Here, we developed a ROS nanopurifier (CSVNP), which was prepared by loading superoxide dismutase (SOD), catalase (CAT) and vancomycin into nanogels through <em>in-situ</em> polymerization. CSVNP can effectively increase enzyme loading and stability, and improve cascade reaction efficiency between enzymes through nanosize effect, so that CSVNP can use a variety of ROS (H₂O₂ and ·O₂^-) as oxygen sources to generate much oxygen <em>in situ,</em> which can effectively alleviate the hypoxic environment and inflammatory response of diabetic tissues, theraby promoting cell migration and angiogenesis, and accelerating wound healing. In addition, the generated oxygen can further promote the transformation of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages and reduce pro-inflammatory factors (TNF-α, IL-6, and IL-1β) release. CSVNP can also effectively eradicate MRSA by releasing vancomycin, preventing bacterial infection from exacerbating the deterioration of diabetic wounds. This multifunctional ROS nanopurifier with antiphlogosis, antibacterial and <em>in-situ</em> oxygen supply, provides a new strategy with universal and translational prospects for clinical diabetic tissue damage.</div></div><div><h3>Statement of Significance</h3><div>Methicillin-resistant staphylococcus aureus (MRSA)-infected diabetic wounds face significant challenges in clinical care, characterized by high ROS levels, acute inflammation, vascular lesions, and hypoxia, which impede healing and risk severe complications. Here, we originally developed a reactive oxygen species (ROS) nanopurifier prepared by <em>in-situ</em> polymerization of superoxide dismutase (SOD), catalase (CAT), and vancomycin. It uses SOD and CAT to continuously convert ROS (H₂O₂ and ·O₂^-) into O₂ in diabetic tissues, effectively improving hypoxia and chronic inflammation, thereby promoting angiogenesis and cell proliferation and migration, and accelerating diabetic wound healing. Vancomycin can effectively kill MRSA bacteria, avoid bacterial infection spread, and reduce complications risk. This safe, efficient and easy-to-prepare ROS nanopurifier provides a general strategy for repairing MRSA-infected diabetic tissue damage.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 334-347"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873647","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":"A metal-organic framework functionalized CaO2-based cascade nanoreactor induces synergistic cuproptosis/ferroptosis and Ca2+ overload-mediated mitochondrial damage for enhanced sono-chemodynamic immunotherapy","authors":"Cong Tang ,&nbsp;Kairui Liu ,&nbsp;Xiaoning Gao ,&nbsp;Hanmeixuan Kang ,&nbsp;Weijie Xie ,&nbsp;Jin Chang ,&nbsp;Linling Yin ,&nbsp;Jun Kang","doi":"10.1016/j.actbio.2024.12.010","DOIUrl":"10.1016/j.actbio.2024.12.010","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Cuproptosis is an emerging form of programmed cell death and shows enormous prospect in cancer treatment. Excessive generation of reactive oxygen species (ROS), metal ion accumulation, and the tricarboxylic acid (TCA) cycle collapse are pivotal elements in the triggering of cell death via mitochondrial pathways. Herein, a cascade nanoreactor CaCuZC has been constructed by incorporating nanosonosensitizer IR780 carbon dots (IR780 CD) and calcium peroxide (CaO&lt;sub&gt;2&lt;/sub&gt;) into metal-organic frameworks (MOF) for synergistic cuproptosis–ferroptosis and Ca&lt;sup&gt;2+&lt;/sup&gt;overload mediated immunotherapy. Within tumor cells, CaCuZC dissociates into CaO&lt;sub&gt;2&lt;/sub&gt;, Cu&lt;sup&gt;2+&lt;/sup&gt;and sonosensitizer IR780 CD. The decomposition of CaO&lt;sub&gt;2&lt;/sub&gt; could generate H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; to strengthen the Cu&lt;sup&gt;2+&lt;/sup&gt;-based chemodynamic therapy and Ca&lt;sup&gt;2+&lt;/sup&gt;overload induces amplified intracellular oxidative stress, thus leading to mitochondrial dysfunction. As a result, the combination of Cu&lt;sup&gt;2+&lt;/sup&gt;and Ca&lt;sup&gt;2+&lt;/sup&gt; overload together induce cascade mitochondrial damage. Moreover, the sonosensitizer IR780 CD generates ROS under ultrasound irradiation to amplify intracellular oxidative stress. In addition, the overloaded Cu&lt;sup&gt;2+&lt;/sup&gt; released from CaCuZC leads to the aggregation of lipoylated protein dihydrolipoamide S-acetyltransferase, thus resulting in cuproptosis. Furthermore, ferroptosis could been concomitantly induced by CaCuZC with intracellular glutathione (GSH) consumption and lipid peroxidation (LPO) accumulation. The cuproptosis–ferroptosis and Ca&lt;sup&gt;2+&lt;/sup&gt;overload-enhanced synergistic therapy also activates robust immunogenic cell death. CaCuZC enhances the infiltration and activation of tumor-specific cytotoxic T cells to transform a “cold” tumor into a “hot” tumor, activating the anti-tumor immune response. This study provides a cascade of mitochondrial damage strategy for triggering cuproptosis–ferroptosis and Ca&lt;sup&gt;2+&lt;/sup&gt;overload-enhanced immunotherapy and achieving improved therapeutic effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;To improve the efficacy of tumor immunotherapy, a cascade nanoreactor CaCuZC was successfully constructed based on a self-assembly strategy for cuproptosis–ferroptosis and Ca&lt;sup&gt;2+&lt;/sup&gt; overload mediated immunotherapy. Upon decomposition within the acidic and GSH-overexpressing tumor microenvironment, CaCuZC released CaO&lt;sub&gt;2&lt;/sub&gt; and Cu&lt;sup&gt;2+&lt;/sup&gt; and sonosensitizer IR780 CD. The CaO&lt;sub&gt;2&lt;/sub&gt; further produced H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;/O&lt;sub&gt;2&lt;/sub&gt; and Ca&lt;sup&gt;2+&lt;/sup&gt; in a weakly acidic environment to strengthen the Cu&lt;sup&gt;2+&lt;/sup&gt;-based CDT and IR780 CD-mediated SDT, respectively. The overload copper ions not only led to cuproptosis, but also efficiently induced ferroptosis. The cuproptosis–ferroptosis and Ca&lt;sup&gt;2+&lt;/sup&gt;overload-enhanced synergistic therapy also activates robust immunogenic cell death. This study presents a cascade of mitochondrial d","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 455-473"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788081","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":"Dually functionalized dendrimer for stimuli-responsive release of active ingredients into the skin","authors":"Orikeda Trashi ,&nbsp;Neha Satish ,&nbsp;Ikeda Trashi ,&nbsp;Laurel M. Hagge ,&nbsp;Yalini H. Wijesundara ,&nbsp;Connie Hu ,&nbsp;Fabian C. Herbert ,&nbsp;Ronald A. Smaldone ,&nbsp;Jeremiah J. Gassensmith","doi":"10.1016/j.actbio.2024.12.035","DOIUrl":"10.1016/j.actbio.2024.12.035","url":null,"abstract":"<div><div>The skin, our largest organ, protects against environmental dangers but is vulnerable to various conditions like infections, eczema, dermatitis, psoriasis, skin cancer, and age-related collagen and elastin degradation. Its outer layer, the water-impermeable epidermis, presents challenges for passive drug delivery to the lower living layers of the skin. An ideal dermal delivery system should penetrate the epidermis and release treatments over time. We report a stimuli-activated nanocarrier that slowly releases active ingredients under skin-specific conditions. Using a fourth-generation polyamidoamine (PAMAM), dendrimer functionalized with poly(2-ethyl-2-oxazoline) and palmitoyl pentapeptide-4, we show a controlled release of biologically active therapeutics into the dermis of the skin for 24 h. <em>Ex vivo</em> studies demonstrate that our nanocarrier system delivers cargo to the dermis and is non-toxic to skin fibroblasts. As a proof of principle, we demonstrate a system that effectively enhances collagen production in human dermal fibroblasts by co-delivering all-trans retinol and palmitoyl pentapeptide-4. Our nanosystem surpasses the effects of individual components. This nanocarrier offers a promising approach for targeted dermal delivery, potentially improving treatment efficacy for various skin conditions while minimizing adverse effects associated with traditional formulations.</div></div><div><h3>Statement of Significance</h3><div>In this manuscript we introduce a stimuli-responsive nanocarrier based on a G4-PAMAM dendrimer functionalized with poly(2-ethyl-2-oxazoline) (POZ) and palmitoyl pentapeptide-4, designed to deliver biomolecules specifically to the skin. The nanocarrier enables controlled, stimuli-triggered release under skin-specific conditions (pH 5, 37 °C), enhancing dermal penetration and minimizing release at neutral pH or lower temperatures. This work improves traditional dendrimer systems by reducing toxicity through POZ, ensuring controlled delivery without invasive techniques like iontophoresis, and co-delivering both a small molecule (all-trans-retinol) and a collagen-stimulating peptide for enhanced therapeutic effects. This system addresses major drug delivery challenges, sets a new precedent for safer, multifunctional nanomaterials, and advances dendrimer chemistry, opening new possibilities in targeted therapies, skin treatments, and materials science.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 571-583"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856868","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":"Regulation of antigen presentation and interleukin 10 production in murine dendritic cells via the oxidative stimulation of cell membrane using a polycation-porphyrin-conjugate-immobilized cell culture dish","authors":"Van Thi Hong Doan ,&nbsp;Takashi Imai ,&nbsp;Naoki Kawazoe ,&nbsp;Guoping Chen ,&nbsp;Toru Yoshitomi","doi":"10.1016/j.actbio.2025.01.004","DOIUrl":"10.1016/j.actbio.2025.01.004","url":null,"abstract":"<div><div>Tolerogenic dendritic cells with professional antigen presentation <em>via</em> major histocompatibility complex molecules, co-stimulatory molecules (CD80/86), and interleukin 10 production have attracted significant attention as cellular therapies for autoimmune, allergic, and graft-versus-host diseases. In this study, we developed a cell culture dish equipped with polycation-porphyrin-conjugate-immobilized glass (PA-HP-G) to stimulate immature murine dendritic cell (iDCs). Upon irradiation with a red light at 635 nm toward the PA-HP-G surface, singlet oxygen was generated by the immobilized porphyrins on the PA-HP-G surface. When iDCs were cultured on the PA-HP-G surface, moderate light irradiation generated lipid radicals without excessive generation of reactive oxygen species in the cytoplasm and nucleus, which led to the oxidative stimulation of the iDC cell membrane without cell death. Light irradiation changed the morphology of dendritic cells on the PA-HP-G surface to a tree-like structure with dendrites, accelerated their maturation, and enhanced the antigen-presenting ability for the ovalbumin peptide <em>via</em> major histocompatibility complex class I molecules. Additionally, the antigen-presenting dendritic cells on the PA-HP-G surface produced the anti-inflammatory cytokine interleukin 10 upon light irradiation. These results indicated that upon moderate light irradiation, the PA-HP-G surface regulated the maturation of iDCs into tolerogenic dendritic cells.</div></div><div><h3>Statement of Significance</h3><div>• Cell culture dish is developed for selective oxidative stimulus of cell membrane.</div><div>• ¹O₂ is generated from polycation/porphyrin-immobilized glass by light irradiation.</div><div>• Lipid radicals are generated without generation of ROS in cytoplasm and nuclei.</div><div>• Immature dendritic cells are maturated by oxidative stimulation of cell membrane.</div><div>• Oxidative membrane stimulus enhances antigen-presentation and IL-10 secretion.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 231-241"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960194","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":"Injectable antibacterial drug-free hydrogel dressing enabled by a bioactive peptide-mimicking synthetic peptidyl polymer","authors":"Rong Zhang ,&nbsp;Yongchang Tian ,&nbsp;Jiaming Cui ,&nbsp;Ian W Hamley ,&nbsp;Chunsheng Xiao ,&nbsp;Li Chen","doi":"10.1016/j.actbio.2025.01.008","DOIUrl":"10.1016/j.actbio.2025.01.008","url":null,"abstract":"<div><div>The management of bacterial wounds presents a significant challenge in the field of medicine and poses a grave threat to public health. Traditional gauze materials exhibit limited efficacy in treating bacterial infection wounds, while antibiotics demonstrate cytotoxicity and resistance. Therefore, in this study, the peptide biomimetic polymer (PAL-BA) was designed and served as the antibacterial framework for constructing an antibiotic drug-free antibacterial hydrogel dressing through a Schiff base reaction with oxidized hyaluronic acid (OHA). The design of PAL-BA aims to emulate the antimicrobial properties of host defense peptides, serving as a viable alternative to antibiotics drugs. It exhibits comparable antimicrobial activity to polylysine while maintaining biosafety. <em>In vitro</em> experiments demonstrated that PAL-BA exhibited exceptional antibacterial activity against both <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>, while the PAL-BA based antibacterial hydrogel (PBP gel) effectively eliminated 100% of pathogenic bacteria within a duration of 140 min. <em>In vivo</em> studies further demonstrated that PBP hydrogels effectively accelerate the healing of bacterial infected wounds by blocking the infection process. Therefore, the antimicrobial peptide biomimetic polymer hydrogel exhibits significant promise for the management of bacterial wound infections.</div></div><div><h3>Statement of significance</h3><div>The management of bacterial infection wounds remains a challenging issue in clinical practice. In this study, we propose the utilization of a peptide biomimetic polymer (PAL-BA) as an antibacterial framework and its combination with oxidized hyaluronic acid (OHA) through Schiff base reactions to develop an antibiotic drug-free antibacterial hydrogel dressing for the treatment of bacterial infections wounds. The design of PAL-BA aims to mimic the antimicrobial properties of host defense peptides, providing a promising alternative to antibiotic drugs. It demonstrates comparable antimicrobial activity to poly-lysine while maintaining biosafety. Importantly, this antimicrobial peptide biomimetic polymer hydrogel effectively inhibits the infection process in mouse wounds and accelerates the healing of bacterially infected wounds, offering a therapeutic approach for treating infected wounds.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 143-156"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967421","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":"Macrophage membrane-camouflaged pure-drug nanomedicine for synergistic chemo- and interstitial photodynamic therapy against glioblastoma","authors":"Wei Cheng ,&nbsp;Zhiran Duan ,&nbsp;Han Chen,&nbsp;Yanjun Wang,&nbsp;Chao Wang,&nbsp;Yuqing Pan,&nbsp;Jie Wu,&nbsp;Ning Wang,&nbsp;Haijing Qu,&nbsp;Xiangdong Xue","doi":"10.1016/j.actbio.2025.01.016","DOIUrl":"10.1016/j.actbio.2025.01.016","url":null,"abstract":"<div><div>Glioblastoma (GBM) persists as a highly fatal malignancy, with current clinical treatments showing minimal progress over years. Interstitial photodynamic therapy (iPDT) holds promise due to its minimally invasive nature and low toxicity but is impeded by poor photosensitizer penetration and inadequate GBM targeting. Here, we developed a biomimetic pure-drug nanomedicine (MM@CT), which co-assembles the photosensitizer chlorin e6 (Ce6) and the first-line chemotherapeutic drug (temozolomide, TMZ) for GBM, then camouflaged with macrophage membranes. This design eliminates the need for traditional excipients, ensuring formulation safety and achieving exceptionally high drug loading with 73.2 %. By leveraging the biomimetic properties of macrophage membranes, MM@CT evades clearance by the mononuclear phagocyte system and can overcome blood circulatory barriers to target intracranial GBM tumors due to its inherent tumor-homing ability. Consequently, this targeted strategy enables precise delivery of TMZ to the tumor site while significantly enhancing Ce6 accumulation within the tumor tissue. Upon intra-tumoral irradiation using an optical fiber, activated Ce6 synergizes with TMZ to exert both cytotoxic effects from chemotherapy and unique advantages from iPDT simultaneously attacking GBM tumors in a dual manner. In subcutaneous and intracranial GBM mouse models, MM@CT exhibits remarkable anti-tumor efficacy with minimal systemic toxicity, emerging as a promising GBM treatment strategy.</div></div><div><h3>Statement of significance</h3><div>Glioblastoma (GBM) remains a formidable brain cancer, posing significant therapeutic challenges due to the presence of the blood-brain barrier (BBB) and tumor heterogeneity. To overcome these obstacles, we have developed MM@CT, a biomimetic nanomedicine with exceptional drug loading efficiency of 73.2 %. MM@CT incorporates the photosensitizer Ce6 and chemotherapy agent TMZ, encapsulated within nanoparticles and camouflaged with macrophage membranes. This innovative design enables efficient BBB penetration, precise tumor targeting, and synergistic application of chemotherapy and photodynamic therapy. Encouragingly, preclinical evaluations have demonstrated substantial antitumor activity with minimal systemic toxicity, positioning MM@CT as a promising therapeutic strategy for GBM.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 392-405"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973715","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}