Acta biomaterialia最新文献

{"title":"Phosphorous dendrimer-mediated biomineralization for synergistic blockade therapy and hypoxia-activated chemotherapy of tumors.","authors":"Jiajia Liang, Huxiao Sun, Jingjing Li, Yifan Huang, Yu Zou, Serge Mignani, Jean-Pierre Majoral, Xiangyang Shi, Mingwu Shen","doi":"10.1016/j.actbio.2025.04.038","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.038","url":null,"abstract":"<p><p>Blockade therapy involving the artificial induction of biomineralization in tumor tissues has emerged as a promising strategy for treating malignant tumors. However, standalone blockade therapy which merely obstructs tumor growth rather than directly destroying the tumors is quite limited in therapeutic efficacy. Herein, we report the phosphite-terminated phosphorus dendrimers (AK176)/fibronectin (FN) nanocomplexes (NCs) with tumor-targeting and biomineralization-inducing properties to encapsulate a hypoxia-activated tirapazamine (TPZ) to achieve synergistic blockade therapy/chemotherapy of triple-negative breast cancer (TNBC). The constructed AK176@FN/TPZ (AFT) NCs exhibit a spherical shape with a size of 134.1 nm and good colloidal stability, can target tumor cells through specific recognition between the Arg-Gly-Asp sequence of FN and α_vβ₃ integrin receptors, and specifically induce mineral deposition on cancer cytomembranes by means of the inherent calcium ion adsorption property of dendrimers. Notably, the AFT-mediated biomineralization can generate tumor hypoxia and amplify the chemotherapeutic effect of TPZ, thereby effectively inhibiting tumor cell proliferation and lung metastasis through synergistic blockade therapy/chemotherapy in an orthotopic TNBC xenograft model. The developed AFT NCs with a simple composition represent an advanced nanomedicine formulation that can induce synergistic tumor-targeting blockade therapy and chemotherapy, which may be extended to tackle other cancer types. STATEMENT OF SIGNIFICANCE: Blockade therapy involving the artificial induction of biomineralization in tumor tissues has emerged as a promising strategy for treating malignant tumors. Herein, phosphite-terminated phosphorus dendrimers (AK176)/fibronectin (FN) nanocomplexes (NCs) with tumor-targeting and biomineralization-inducing properties are developed to encapsulate a hypoxia-activated drug tirapazamine (TPZ), resulting in synergistic blockade therapy/chemotherapy of triple-negative breast cancer in a mouse model. The developed AK176@FN/TPZ (AFT) NCs can target tumor cells through specific recognition between the Arg-Gly-Asp sequence of FN and α_vβ₃ integrin receptors, and specifically induce mineral deposition via the inherent calcium ion adsorption property of bisphosphonate groups of dendrimers, thereby triggering tumor biomineralization for blockade therapy. The AFT-mediated biomineralization on tumor cell membranes generates tumor hypoxia, which further amplifies the chemotherapeutic effect of TPZ.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dissolvable microneedle platform for the delivery of tumor-derived total RNA nanovaccines for enhanced tumor immunotherapy.","authors":"Jiachen Wang, Sicong Huang, Huiye Wei, Simin Liang, Yuan Ding, Zecong Xiao, Xintao Shuai","doi":"10.1016/j.actbio.2025.04.039","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.039","url":null,"abstract":"<p><p>Tumor-derived total RNA (TdRNA) vaccines induce broad immune responses by either synthesizing tumor-specific antigens or activating pattern recognition receptors, making them a promising tool in cancer immunotherapy for the activation of cytotoxic T lymphocytes (CTLs). However, TdRNA vaccines face issues such as low stability and inadequate immune activation. To overcome these challenges, we have developed a dissolvable microneedle delivery platform, PTC NVs@MNs, designed for the simultaneous delivery of TdRNA and CpG oligodeoxynucleotides (CpG ODN). This platform stabilizes TdRNA, maintaining its activity for up to 30 days at room temperature and promotes dendritic cell maturation, and then activates T lymphocyte-mediated antitumor immunity through the targeted delivery of TdRNA and CpG. PTC NVs@MNs not only enhance dendritic cell maturation and increase CD8⁺ T cell infiltration into tumors, eliciting robust antitumor immune responses that inhibit tumor growth, but also induce antitumor immune memory to prevent tumor development. This innovative approach offers therapeutic and preventive benefits in tumor management. STATEMENT OF SIGNIFICANCE: Tumor-derived total RNA (TdRNA) holds potential for eliciting a broad immune response; however, its therapeutic efficacy against triple-negative breast cancer (TNBC) is constrained by low stability and inadequate immune activation. To overcome these limitations, we engineered a dissolving microneedle patch for transdermal co-delivery of TdRNA and CpG oligodeoxynucleotides (CpG ODN). This system not only stabilizes TdRNA-maintaining its bioactivity for 30 days at room temperature-but also promotes dendritic cell maturation and activates T lymphocyte-mediated antitumor immunity . This study demonstrated that the well-designed microneedle patch effectively prevents RNA degradation without requiring stringent storage conditions, offering both therapeutic and preventive benefits in tumor management.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterising epi-perineurial barrier function by microscale techniques including a miniaturised Ussing chamber.","authors":"S M Krug, I M Lee, L Knobe, B Hartmannsberger, M S Atalla, H L Rittner, M Fromm","doi":"10.1016/j.actbio.2025.04.043","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.043","url":null,"abstract":"<p><p>Barriers of peripheral nerves, like the sciatic nerve, are complex structures, consisting of the inner endoneurial capillary barriers and the outer epi‑ and perineurial layers. The latter two, collectively also known as epi‑perineurium (EPN), are necessary for maintenance of the nerve homeostasis. However, the involvement of the EPN in altered nerve conduction in neuropathy is not well-understood. To date, reliable data on barrier properties and ion permeabilities have been limited by the difficulty of accessing the barrier experimentally. For analysing the EPN of rat sciatic nerves, we developed a preparation technique and a miniaturised (area 0.6 mm²), though edge damage-free, Ussing chamber. Electrophysiological characterisation included measurement of transepiperineurial resistance, differentiation of para- and transcellular contributions to this by two-path impedance spectroscopy and determination of permeabilities for flux markers and for ions by dilution and bi-ionic potential measurements.We found the EPN being definable as tight and responsive to changes in the gradients between the endoneurial and the extra-nerval compartment. In a rat model of bortezomib (Bortezomib)-induced polyneuropathy, we demonstrate the EPN to be impaired with a specific increase in potassium permeability, which normalises with the recovery of the animals.In conclusion, we present an advanced, dependable method to analyse the EPN, which can be extended to other microscale epi‑ or endothelia. Functionally, we demonstrate with this technique that the EPN forms a crucial and specific barrier to maintain ion gradients within the sciatic nerve. STATEMENT OF SIGNIFICANCE: We developed a miniaturized Ussing chamber allowing precise electrophysiological analysis of microscale barrier tissues, avoiding edge damage and experimental interferences. Using this, we characterized the epi‑perineurium (EPN) barrier of sciatic nerves, demonstrating it to be a tight and responsive barrier, essential for maintaining ion balance within that nerve. In a neuropathy model, we identified impaired potassium permeability during hyperalgesia, which normalized with recovery. Beyond the EPN, this method is broadly applicable to other previously inaccessible microscale barriers, enabling advanced studies of barrier (patho)physiology. Our work bridges biomaterial development and tissue barrier research, providing detailed insights into ion and solute transport, and may be used to study regulatory mechanisms and the subsequent development of potential therapeutic strategies such as targeted drug delivery across these barrier tissues.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetothermal and ultrasound-activated nanoplatform for the inhalable therapy of bacterial lung infections.","authors":"Shuai Zhang, Yundi Wu, Chaoyi Lyu, Huanran Qu, Xilong Wu","doi":"10.1016/j.actbio.2025.04.041","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.041","url":null,"abstract":"<p><p>Antibiotic resistance in Klebsiella pneumoniae infections presents significant challenges in treating lung inflammation. To overcome tissue penetration barriers and modulate inflammatory responses, innovative therapeutic approaches are essential. This study introduces an inhalable nanoplatform, Fe_xS_y:Gd@PVP (FGP), based on polyvinylpyrrolidone-modified gadolinium-doped nonstoichiometric iron sulfide nanostructures. The platform integrates synergistic magnetic-ultrasound activation with magnetothermal therapy (mMHT), sonodynamic therapy (SDT), and gas therapy (GT) for targeted bacterial lung infection treatment. Gadolinium incorporation enhances the magnetothermal activation, improving magnetothermal conversion efficiency and sonodynamic performance by increasing magnetic anisotropy, narrowing the semiconductor bandgap, and enriching sulfur vacancies. Delivered via nebulized inhalation, FGP reaches infected lung tissues noninvasively. Exposure to alternating magnetic fields (AMF) and ultrasound (US) generates localized heat and reactive oxygen species (ROS), effectively eliminating bacteria. Simultaneously, AMF and US trigger hydrogen sulfide (H₂S) release in the acidic microenvironment, reducing inflammation by inhibiting inflammatory factors such as TNF-α and IL-1β through suppression of STAT3 and ERK phosphorylation. This magnetic-ultrasound co-activated inhalable nanoplatform offers a powerful multimodal therapeutic strategy for overcoming clinical challenges associated with bacterial lung infections. STATEMENT OF SIGNIFICANCE: This study introduces an inhalable nanoplatform that effectively treats multidrug-resistant Klebsiella pneumoniae lung infections. By integrating magnetothermal, sonodynamic, and gas therapies, this system eradicates bacteria and reduces inflammation. It uses gadolinium-doped iron sulfide nanostructures to enhance heat, reactive oxygen species, and hydrogen sulfide production, targeting deep lung infections precisely. Unlike traditional antibiotics, this noninvasive approach has minimal side effects and addresses both bacterial clearance and inflammation. This innovative strategy offers a promising solution for antibiotic-resistant infections and could revolutionize respiratory disease management.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A smart capsule with a bacteria- and pH-triggered enteric polymer coating for targeted colonic microbiome sampling.","authors":"Devendra Sarnaik, Akshay Krishnakumar, Sina Nejati, Caitlyn R Sullivan, Tzu-Wen L Cross, Wayne W Campbell, Jay S Johnson, Rahim Rahimi","doi":"10.1016/j.actbio.2025.04.025","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.025","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The gut microbiome is recognized as a critical factor in advancing precision nutrition and medicine for health and in developing dietary recommendations and targeted therapies for gastrointestinal (GI) health and diseases. However, conventional sampling methods, such as fecal analysis and colonoscopy, often fail to capture microbial information from specific regions of the GI tract or require invasive procedures, thereby limiting accuracy and clinical utility. As a non-invasive alternative, passive sampling capsules have been developed for site-specific microbiome analysis by employing pH-sensitive enteric coatings that delay sampling until the capsule reaches the targeted intestinal region. Although this approach has been successful in the small intestine, colonic sampling remains challenging due to the high interpersonal variability in intestinal pH, which makes it difficult to rely solely on a pH-triggering mechanism. To overcome this challenge, a dual bacterially and pH triggered polymeric enteric coating was created by blending lactulose and N,N-dimethylaminoethyl methacrylate, enabling complete dissolution within the colonic region. Through systematic characterization of multiple polymer blend compositions using Fourier Transform Infrared Spectroscopy, Thermogravimetric Analysis, and Differential Scanning Calorimetry, an optimized design was identified that provides both suitable physical integrity and rapid (∼2 h) degradation in the presence of colonic bacteria, across a pH range of 5 to 8. The optimized blend was subsequently applied as a double-layer enteric coating on a sampling capsule, enabling the dissolution of the outer layer in the small intestine and complete dissolution of the inner layer in the colon. In-vitro and in-vivo pig model studies were conducted to validate the capsule's sampling performance and to ensure the preservation of the microbial environment. Furthermore, 16S rRNA sequencing revealed a taxonomic similarity between samples collected by the capsule and the colonic microbiome (residing between the ileum and fecal matter). Overall, this technology provides an effective approach to targeted microbial sampling and may pave the way for more comprehensive colonic microbiome analyses and improved diagnostic capabilities for GI diseases. STATEMENT OF SIGNIFICANCE: Precise monitoring of the gut microbiome is vital for understanding health and disease, yet current sampling techniques often lack precision or require invasive procedures. Our work introduces a novel, non-invasive capsule that targets the colon using a dual-trigger polymer system activated by both pH and colonic bacteria. This design enables localized sampling of gut microbiota, overcoming the limitations of fecal analysis, endoscopy, and earlier pH-triggered capsule designs. By capturing microbial communities directly from the colon, our technology provides deeper insights into colonic health and conditions such as inflammatory bowel disease and colore","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogels with multiple RGD presentations increase cell adhesion and spreading.","authors":"Abolfazl Salehi Moghaddam, Katelyn Dunne, Wendy Breyer, Yingjie Wu, E Thomas Pashuck","doi":"10.1016/j.actbio.2025.04.037","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.037","url":null,"abstract":"<p><p>A key challenge in designing hydrogels for cell culture is replicating the cell-matrix interactions found in tissues. Cells use integrins to bind their local matrix and form adhesions in which integrins dynamically move on the cell membrane while applying significant forces to the local matrix. Identifying the important biomaterial features for these interactions is challenging because it is difficult to independently adjust variables such as matrix stiffness, stress relaxation, the mobility of adhesion ligands, and the ability of these ligands to support cellular forces. In this work, we designed a hydrogel platform consisting of interpenetrating polymer networks of covalently crosslinked poly(ethylene glycol) (PEG) and self-assembled peptide amphiphiles (PA). We can tune the viscoelasticity of the hydrogel by modulating the composition of both networks. Ligand mobility can be adjusted independently of the matrix mechanical properties by attaching the arginine-glycine-aspartic acid (RGD) cell adhesion ligand to either the covalent PEG network, the dynamic PA network, or both networks at once. We find that endothelial cell adhesion formation and spreading is maximized in soft gels in which adhesion ligands are present on both the covalent and non-covalent networks. The dynamic nature of adhesion domains, coupled with their ability to exert substantial forces on the matrix, suggests that having different presentations of RGD ligands which are either mobile or capable of withstanding significant forces is needed to mimic different aspects of complex cell-matrix adhesions. These results will contribute to the design of hydrogels that better recapitulate physiological cell-matrix interactions. STATEMENT OF SIGNIFICANCE: Creating artificial environments that accurately mimic how cells interact with their surrounding matrix in natural tissues remains a fundamental challenge in biomaterials science. This study introduces a dual-network hydrogel platform that independently controls mechanical properties and adhesion ligand mobility by combining stable and dynamic polymer networks. A significant body of work has shown that matrix viscoelasticity and adhesion ligand mobility are important for cell adhesion and spreading. Our work builds on this by showing that endothelial cells function optimally when they can simultaneously engage with both mobile adhesion sites and force-resistant anchoring points, independent of matrix viscoelasticity. These insights will guide the design of more physiologically relevant hydrogels for tissue engineering applications and disease modeling.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-like cell membrane-coated molybdenum-based nanoclusters for reduced oxidative stress and enhanced neurological recovery after intracerebral hemorrhage.","authors":"Canxin Xu, Yikui Liu, Yuanbo Pan, Hongchi Zhang, Yuhao Sun, Juan Li, Aiguo Wu, Liuguan Bian","doi":"10.1016/j.actbio.2025.04.035","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.035","url":null,"abstract":"<p><p>Excessive reactive oxygen species (ROS) are detrimental to the brain that can result in neurological impairment and inhibiting neurological functionals recovery after intracerebral hemorrhage (ICH). However, there is still a lack of effective treatment for ICH, either with medicine or neurosurgery. Nanozymes with excellent superoxide dismutase and catalase properties can scavenge ROS and may provide therapeutic opportunities for ICH patients. However, the ability of nanozymes to non-invasively target cerebral hemorrhage lesions and further antioxidation effect are still unknown. Herein, neutrophile membrane-disguised molybdenum-based polyoxometalate nanozymes (POM@Mem) were developed to alleviate oxidative stress after ICH. Coating with neutrophil membrane allowed POM to target the hemorrhage sites and further inhibit ROS generation. POM@Mem can improve neuroinflammatory microenvironment and promote behavioral improvement of ICH mouse. Combining neutrophile membrane and nanozymes for targeting brain hemorrhage sites provides an effective strategy for the treatment of ICH. STATEMENT OF SIGNIFICANCE: Excessive reactive oxygen species (ROS) are detrimental to the brain and can lead to neurological impairment, hindering the recovery of neurological functions after intracerebral hemorrhage (ICH). Despite this, effective treatments for ICH, whether pharmaceuticals or neurosurgery, remain scarce. In this study, we developed neutrophil membrane-disguised molybdenum-based polyoxometalate nanozymes (POM@Mem) as a novel approach to alleviate oxidative stress following ICH. The neutrophil membrane coating enabled the POM nanozymes to specifically target hemorrhagic sites, thereby inhibiting ROS production. Additionally, POM@Mem improved the neuroinflammatory microenvironment and facilitated behavioral recovery in ICH mice. The combination of neutrophil membranes and nanozymes for targeted delivery to brain hemorrhage sites offers a promising strategy for the treatment of ICH.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet membrane-camouflaged bioactive glass nano-formulations for enhanced drug delivery in the treatment of acute arterial thrombosis.","authors":"Minglin Ji, Qinying Tang, Olanrewaju Yaasir Olatunji, Rufei Ge, Yue Ying, Jianwei Pan, Khaydar E Yunusov, Guohua Jiang","doi":"10.1016/j.actbio.2025.04.036","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.036","url":null,"abstract":"<p><p>Thrombus treatment remains a significant challenge, primarily due to factors such as the short half-life of thrombolytic agents, suboptimal drug utilization, and limited therapeutic efficacy. In this study, we developed a platelet membrane-camouflaged bioactive glass nanoparticles (BGs) as drug carriers to load thrombolytic agent urokinase (UK) and anticoagulant drug tirofiban (TF). UK and TF were firstly incorporated onto BGs, and followed by a camouflage of polydopamine (PDA) and platelet membrane (PM) to form composite nano-formulation (TUBGs@PP). This composite nano-formulation leverages the PM camouflage to enhance its biocompatibility, prolong circulation time in vivo, and extend the half-life of drugs. Additionally, as-fabricated TUBGs@PP composite nano-formulation can circumvent immune system-mediated clearance, thereby facilitating targeted drug delivery to the thrombus sites and enhancing the thrombolytic efficacy. In vivo results demonstrated that the TUBGs@PP composite nano-formulations not only prolonged circulation time but also effectively unclogged blood vessels at the site of thrombosis, while reducing recurrence of thrombosis and drug side effects. STATEMENT OF SIGNIFICANCE: The platelet membrane-camouflaged bioactive glass nanoparticles as drug carriers for the synergistic co-delivery of urokinase and tirofiban have been developed (TUBGs@PP) for the treatment of acute arterial thrombosis. This cutting-edge therapeutic strategy addresses several critical limitations inherent in current thrombolytic treatments, including the transient half-life of thrombolytic agents, suboptimal drug bioavailability, and limited therapeutic efficacy. In vivo studies demonstrate that TUBGs@PP not only achieves sustained circulation but also effectively restores vascular patency at thrombotic loci, concurrently reducing the risk of thrombotic recurrence and minimizing adverse drug effects. This study highlights the paradigm-shifting potential of TUBGs@PP in thrombolytic therapy, offering a transformative solution to existing challenges and promising to markedly improve clinical outcomes for patients.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous nanoplatforms for tumor photoimmunotherapy: Hypoxia modulation and STING pathway activation.","authors":"Yongqing Yang, Ni Shao, Qiao Luo, Nianlan Cheng, Jifeng Chen, Yanyu Huang, Cuiqing Huang, Jiang Ouyang, Liangping Luo, Zeyu Xiao","doi":"10.1016/j.actbio.2025.04.030","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.030","url":null,"abstract":"<p><p>Photoimmunotherapy (PIT) holds significant promise for cancer treatment due to its spatial precision and sustained therapeutic effects. However, overcoming the immunosuppression and hypoxia of the tumor microenvironment (TME) remains a major challenge. To solve this problem, we developed a multifunctional PIT nanoplatform (BYMnNps). Its composition plays different roles: i) Biliverdin can induce mild photothermal and photodynamic therapy, enhance the penetration of nanoplatforms into tumors, and induce immunogenic cell death; ii) the immunotherapy peptide tyroserleutide induces tumor cell apoptosis and enhances tumor-specific immune responses; iii) Mn²⁺ can catalyze the generation of oxygen from hydrogen peroxide, reducing tumor hypoxia, while activating the cGAS-STING pathway, further boosting cancer immunotherapy. The nanoplatforms significantly inhibit tumor growth and increase tumor sensitivity to α-PD 1 therapy. Notably, BYMnNps also exhibit photoacoustic and magnetic resonance imaging capabilities. Overall, BYMnNps effectively counteract tumor immune suppression and alleviates TME hypoxia, demonstrating good biocompatibility and antitumor efficacy, with broad potential for precision cancer treatment guided by multimodal imaging. STATEMENT OF SIGNIFICANCE: Photoimmunotherapy holds great promise for cancer treatment due to its spatial precision and sustained therapeutic effects. However, phototherapy-induced tumor hypoxia leads to resistance, posing a significant challenge. This study utilizes endogenous photosensitizer biliverdin, immunotherapy peptide tyroserleutide, and Mn²⁺ to self-assemble into a multifunctional nanoparticle, aimed at simultaneously reversing the immunosuppression of the tumor microenvironment and alleviating hypoxia. It demonstrates good biosafety and antitumor efficacy, enhancing tumor sensitivity to α-PD1 therapy. Additionally, it exhibits photoacoustic and magnetic resonance imaging capabilities, showing broad potential for precision cancer treatment guided by multimodal imaging. It has the potential to overcome the current limitations of photoimmunotherapy, offering a new avenue for cancer treatment.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming by chemo-gene co-delivery nanoparticles for chemo-immunotherapy in head and neck squamous cell carcinoma.","authors":"Wenqing Zou, Bingyue Huo, Yaqin Tu, Yuhe Zhu, Yuwei Hu, Qianru Li, Xuan Yu, Bo Liu, Wei Tang, Songwei Tan, Hongjun Xiao","doi":"10.1016/j.actbio.2025.04.031","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.031","url":null,"abstract":"<p><p>The therapeutic effects of platinum-based drugs are closely linked to the dysregulation of tumor metabolic-immune microenvironment, particularly aberrant lactate accumulation. Herein, we engineered multifunctional nanoparticles (PPPt^IV NPs) through electrostatic self-assembly of poly(β-amino ester) to co-encapsulate a cisplatin prodrug (Pt^IV) and CRISPR/Cas9-PKM2 plasmids. Mechanistically, PPPt^IV NPs efficiently entered cells via endocytosis, followed by escape from lysosomal degradation and cargo release. The reduction of Pt^IV prodrug to active Pt^II via GSH depletion induced DNA damage and ROS upregulation, thereby triggering apoptosis. Concurrently, CRISPR/Cas9-mediated PKM2 knockdown suppressed the Warburg effect, resulting in reduced lactate production and downregulated expression of HIF-1α and PD-L1. These alterations drove immune microenvironment remodeling through enhanced dendritic cell maturation, polarized M1 macrophages, and altered cytokine profiles (characterized by upregulation of IFN-γ, TNF-α, and IL-12 alongside suppression of IL-10), ultimately activating T cell-mediated antitumor immunity. Compared to conventional cisplatin, PPPt^IV NPs demonstrated superior efficacy against both primary and recurrent tumors while reducing nephrotoxicity through synergistic chemo-immunotherapeutic effects, offering a valuable strategy for HNSCC treatment. STATEMENT OF SIGNIFICANCE: This study engineered an innovative nanoplatform (PPPt^IV) that synergistically integrates a Pt^IV prodrug with a CRISPR/Cas9-PKM2 plasmid for treating head and neck squamous cell carcinoma. By simultaneously enhancing DNA damage and reversing lactate-mediated immunosuppression, PPPt^IV nanoplatform achieved chemo-immunotherapy that showed greater suppression of primary and recurrent tumors with reduced renal toxicity compared to cisplatin. This nanotechnology-driven strategy provides valuable insights into the combination of platinum-based drugs with immunometabolic interventions.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}