{"title":"Enhanced hemocompatibility and cytocompatibility of halloysite nanotubes <i>via</i> the formation of a protein corona.","authors":"Pengfei Ma, Xiangyu Chen, Liming Deng, Kangmao Li, Yue Feng, Mingxian Liu","doi":"10.1039/d6bm01201a","DOIUrl":"https://doi.org/10.1039/d6bm01201a","url":null,"abstract":"<p><p>Halloysite clay nanotubes (HNTs) show promising applications as hemostatic materials and tissue-repairing materials owing to their unique tubular structure and physicochemical properties. When HNTs enter the body, the protein corona formed on HNTs affects the properties and behavior of the nanoparticles. Here, bovine plasma protein was used as a model protein to study the protein corona on HNTs (PC@HNTs), using chitosan-coated HNTs as a control. The formation of a stable protein corona layer on HNTs was confirmed by particle size, surface potential, and morphology, while circular dichroism analysis revealed significant changes in the protein secondary structure. PC@HNTs markedly improved hemocompatibility while retaining appreciable coagulation activity; for example, PC@HNTs-20% exhibited a hemolysis ratio below 1% at 1.5 mg mL<sup>-1</sup>. The protein corona on HNTs also reduced red blood cell deformation, phosphatidylserine externalization, reactive oxygen species generation, Ca<sup>2+</sup> influx, K<sup>+</sup> loss, and hemoglobin release. In RAW264.7 cells, PC@HNTs-20% reduced cellular uptake and oxidative stress while maintaining the cell viability above 85% at 800 μg mL<sup>-1</sup>. All these results demonstrated that the protein corona acts as a protective bio-interface that shields the reactive mineral surfaces, which weakens direct cell-material interactions and prevents harm to the cells. This work suggests that protein corona engineering can improve the biosafety of natural HNTs <i>in vivo</i> while preserving their hemostatic function, which provides evidence for the rational design of safe blood-contacting clay materials.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergistic dual sensitizer integrated ZIF-8 nanoplatform for enhanced sonodynamic eradication of deep-seated drug-resistant biofilms.","authors":"Rongrong Qin, Jiaomei Zhao, Yueshan Hu, Ronghao Lv, Jinwei Hu, Nian Liu, Huimin Cheng, Peng Li, Wei Huang","doi":"10.1039/d6bm00802j","DOIUrl":"https://doi.org/10.1039/d6bm00802j","url":null,"abstract":"<p><p>Deep-seated biofilm infections caused by drug-resistant bacteria, particularly methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), remain a major clinical challenge due to restricted antibiotic penetration, hypoxic microenvironments, and intrinsic tolerance provided by biofilm structures. Sonodynamic therapy (SDT), which utilizes ultrasound (US) to activate sensitizers for reactive oxygen species (ROS) generation, has emerged as a promising modality with advantages such as tissue penetration and biofilm disruption. Nevertheless, sonosensitizers, particularly organic small molecules, are constrained by poor physicochemical stability and inadequate specificity toward infection sites. Here, we present a dual sensitizer integrated sonodynamic agent (DiSONA), engineered by co-encapsulating sonosensitizers Rose bengal and curcumin within a zeolitic imidazolate framework, ZIF-8. The DiSONA exhibits high drug-loading capacity, a positively charged surface that enhances bacterial targeting, and a pH/US-responsive release profile tailored to the acidic infection microenvironments. Upon US exposure, the DiSONA generated substantially higher overall ROS levels than the corresponding single-sensitizer formulations, resulting in potent antibacterial activity against planktonic MRSA and mature MRSA biofilms (>99.999% and >99.9% killing rates, respectively). In a murine subcutaneous abscess model, DiSONA-mediated SDT yielded >99.99% MRSA clearance without observable systemic toxicity. This work establishes a paradigm for combating deep-seated drug-resistant biofilm infections by integrating dual sonodynamic mechanisms with nanocarrier engineering.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Near-infrared-II fluorescent quantum dots for <i>in vivo</i> tracking of colonization dynamics of transplanted gut microbiota.","authors":"Yongxin Zhang, Zhongzhu Mo, Qingping Yang, Bin Jiang, Rui Han, Jinyu Wang, Hanbin Liu, Shaobing Zhou, Jingya Zhao","doi":"10.1039/d6bm01047d","DOIUrl":"https://doi.org/10.1039/d6bm01047d","url":null,"abstract":"<p><p>Faecal microbiota transplantation (FMT) represents a critical therapeutic strategy for diseases associated with gut microbiota dysbiosis, but effective real-time monitoring methods for the dynamic behaviour of transplanted microbiota in the recipient gut are lacking. This study constructed a bacterial labelling probe based on near-infrared-II (NIR-II) fluorescent quantum dots (QDs). Using Ag<sub>2</sub>Te QDs as the fluorescent core, a PLGA-PEG coating was applied to improve their water dispersibility and biocompatibility, while heparin functionalization endowed them with bacterial labelling capabilities. This probe exhibits excellent <i>in vivo</i> and <i>in vitro</i> biosafety and stable NIR-II fluorescence performance, enabling efficient fluorescent labelling of bacteria within the transplanted microbiota. Based on NIR-II <i>in vivo</i> fluorescence imaging technology, real-time dynamic monitoring of FMT transplanted microbiota in the mouse intestine was achieved, and it was revealed that it has a long-term retention characteristic only in the intestine of CDI mice. This study establishes an NIR-II fluorescence imaging strategy for dynamic tracking of the transplanted microbiota during FMT, with potential for investigating its <i>in vivo</i> dynamics.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhanced yields and purity: a robust optimization framework for the production of multifunctional elastin-like proteins.","authors":"Niels Geysmans, Lotte Vastmans, Ruben Verstraete, Xaveer Van Ostade, Virginie Bito, Geert-Jan Graulus","doi":"10.1039/d6bm00527f","DOIUrl":"10.1039/d6bm00527f","url":null,"abstract":"<p><p>Elastin-Like Proteins (ELP) are highly versatile biomaterials with significant potential in tissue-engineering, due to their design flexibility, mechanical properties and tunable stimuli responsiveness. However, expression conditions reported in literature do not always translate to new ELP fusion proteins. This study establishes a methodology to optimize expression conditions for modular ELP constructs with intermittent peptide domains. Response Surface Methodology is employed to systematically optimize protein expression of three distinct ELP constructs (containing either RGD domains, heparin-binding domains, or a combination thereof) currently being explored in the domain of injectable biomaterials. By combining small-scale expression with western blot densitometry, an accessible workflow is established to systematically optimize expression yields while avoiding extensive sample preparation and limiting the number of experiments. Analysis of the lower critical solution temperature of the ELPs suggests a correlation between the molecular architecture and the observed transition temperature. Furthermore, <i>in vitro</i> biocompatibility analyses confirm high cell viability, validating these modular ELPs as promising candidates for injectable hydrogels.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"4875-4885"},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meng Li, Ying Li, Xiangyu Wu, Xueting Li, Heli Gao, Xiang Zhong, Xiaohu Yang, Hao Fei, Chunyan Li, Qiangbin Wang
{"title":"pH-Responsive liposomes co-delivering a membrane-active peptide and the PI3Kγ inhibitor to reconstruct the tumor microenvironment for enhanced antitumor immunotherapy.","authors":"Meng Li, Ying Li, Xiangyu Wu, Xueting Li, Heli Gao, Xiang Zhong, Xiaohu Yang, Hao Fei, Chunyan Li, Qiangbin Wang","doi":"10.1039/d6bm00678g","DOIUrl":"10.1039/d6bm00678g","url":null,"abstract":"<p><p>Immunotherapy has shown enormous promise for cancer treatment, yet its efficacy is often hindered by the highly immunosuppressive tumor microenvironment (TME). Here, we developed a pH-responsive and cRGD-modified multifunctional liposomal system (FP2@PSLR) to co-deliver an immunogenic cytotoxic peptide (FR) and the PI3Kγ inhibitor IPI549 for coordinated TME remodeling. FR induces immunogenic cell death while exerting direct cytolytic activity, whereas IPI549 promotes macrophage repolarization toward the pro-inflammatory M1-like phenotype, enabling synergistic relief of immune suppression. FP2@PSLR, constructed from acid-sensitive lipids <i>via</i> reverse-phase evaporation, exhibited a uniform size (∼156 nm), high encapsulation efficiencies, excellent physiological stability, and rapid drug release under mildly acidic conditions. <i>In vitro</i>, the liposomes showed good biocompatibility, reduced hemolysis, effective immunogenic cell death induction, dendritic cell activation, and macrophage repolarization. In a 4T1 tumor model, FP2@PSLR demonstrated prolonged circulation, strong α<sub>v</sub>β<sub>3</sub> integrin-mediated tumor targeting, and clear NIR-II fluorescence for real-time tracking. Treatment resulted in significant TME reprogramming, including enhanced CD8<sup>+</sup> T-cell infiltration, increased immune memory formation, and potent antitumor effects without systemic toxicity. These findings highlight FP2@PSLR as a rationally engineered nanoplatform capable of enhancing antitumor immunity through multi-pathway modulation of the immunosuppressive TME.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"5046-5062"},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Grace H Nguyen, Everett Grizzle, Elizabeth J Brisbois
{"title":"Slippery bioactive nanoemulsion-infused and nitric oxide-releasing surfaces for anti-fouling biomedical applications.","authors":"Grace H Nguyen, Everett Grizzle, Elizabeth J Brisbois","doi":"10.1039/d6bm00767h","DOIUrl":"10.1039/d6bm00767h","url":null,"abstract":"<p><p>Indwelling medical devices are highly susceptible to infection and thrombosis, two major complications arising from bacterial adhesion, protein deposition, and platelet aggregation on device surfaces. To address these challenges, a multifunctional surface that integrates slippery nanoemulsion (NE) infusion with dual bioactive release of nitric oxide (NO) and eugenol (EG) was developed. <i>N</i>-hexadecane-based NEs, with or without eugenol incorporation, were infused into <i>S</i>-nitroso-<i>N</i>-acetylpenicillamine (SNAP)-impregnated polydimethylsiloxane (PDMS) to create materials featuring a stable lubricant reservoir that provides anti-fouling properties and is combined with an active antimicrobial and antithrombotic agent. The combined material SNAP-2%EG exhibited low sliding angles (<20°) while maintaining near-physiological NO release for 24 h. The SNAP-2%EG did not elicit cytotoxic effects on mouse fibroblast cells, with relative cell viability >70%, while significantly reducing the adhesion and viability of <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> by 2.95 log and 1.76 log, respectively. The combined strategy significantly reduced fibrinogen adsorption by up to 40% and platelet adhesion by 98%, thereby enhancing anti-fouling efficacy. The SNAP-impregnated samples infused with eugenol-NE demonstrated promising results and potential for biomedical applications.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"4915-4931"},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13448801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antonio Martino, Joshua Moskow, Jason Shenoi, Gabrielle Rogie, Nick Sears, Carly S Filgueira
{"title":"Hydrogel systems in orthopedics: delivery modality as a framework for translational design.","authors":"Antonio Martino, Joshua Moskow, Jason Shenoi, Gabrielle Rogie, Nick Sears, Carly S Filgueira","doi":"10.1039/d6bm00766j","DOIUrl":"10.1039/d6bm00766j","url":null,"abstract":"<p><p>Orthopedic diseases impose heterogeneous therapeutic demands, ranging from symptomatic control of inflammation and pain to intra-articular drug delivery, cartilage repair, bone regeneration, and prevention of implant-associated infection. Although hydrogels are widely investigated as tunable biomaterials for these applications, their translational potential is often discussed primarily in terms of polymer composition or crosslinking chemistry. This review argues that delivery modality provides a clinically useful framework for evaluating orthopedic hydrogel systems, but translational success depends on the combined influence of material properties, mechanical requirements, degradation behavior, biological integration, manufacturability, and regulatory feasibility. Hydrogel patches, injectable hydrogels, and implantable hydrogels differ in tissue access, mechanical competence, payload capacity, residence time, invasiveness, and regulatory feasibility. Here, we critically compare these three delivery paradigms across major orthopedic indications. Hydrogel patches are best positioned for localized analgesic and anti-inflammatory therapy but remain poorly suited for deep regenerative delivery because of skin-barrier limitations. Injectable hydrogels can offer a strong balance between minimally invasive administration and localized therapeutic control, particularly for intra-articular disease and irregular defects, but require improved retention, mechanical stability, and predictable gelation. Implantable hydrogels can provide architectural and mechanical control for focal bone and osteochondral repair when designed as structural or composite systems, yet their clinical adoption is constrained by surgical burden, manufacturing complexity, and long-term durability requirements. By shifting the discussion from material cataloguing to indication- and delivery-modality-driven design, this review provides a balanced framework for evaluating orthopedic hydrogel technologies and identifies practical translational priorities related to tissue access, mechanical durability, biological response, manufacturing, and clinical feasibility.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"4769-4798"},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guikang Wang, Xianying Chen, Shiwen Zheng, Yanjiu Li, Zhuowei Shen, Xiaohan Yu, Kun Shang, Jianliu Wang, Xiuli Sun, Di Jia
{"title":"Investigation of <i>in vivo</i> silk scaffold degradation by decoupling tissue ingrowth using a Gaussian process regression-driven digital twin framework.","authors":"Guikang Wang, Xianying Chen, Shiwen Zheng, Yanjiu Li, Zhuowei Shen, Xiaohan Yu, Kun Shang, Jianliu Wang, Xiuli Sun, Di Jia","doi":"10.1039/d6bm00920d","DOIUrl":"10.1039/d6bm00920d","url":null,"abstract":"<p><p>Pelvic organ prolapse (POP) reconstruction is increasingly performed by utilizing knitted silk meshes (KSM), yet tracking <i>in vivo</i> degradation kinetics remains challenging due to complex host tissue integration. This study developed an AI-driven semi-empirical framework utilizing Gaussian Process Regression (GPR) to bridge the kinetic mismatch between <i>in vitro</i> and <i>in vivo</i> environments. KSM scaffolds underwent 32 weeks of accelerated <i>in vitro</i> enzymatic degradation, with morphology (SEM), molecular conformation (FTIR), and mass loss being coupled with mechanical decay to train the GPR model. <i>In vitro</i> results revealed a multi-stage physical disintegration <i>via</i> a topochemical erosion pathway that preserved crystalline β-sheet structures despite macro-scale mass and mechanical loss. When validated in a rat abdominal wall defect model, traditional tracking metrics encountered severe bottlenecks. Heterogeneous dye labeling caused premature fluorescence quenching after 16 weeks, while extensive tissue ingrowth masked gravimetric and SEM signatures. Intriguingly, a bi-phasic <i>in vivo</i> mechanical trajectory was identified, where initial degradation-led failure was followed by a secondary mechanical recovery driven by biomechanical synergy with neo-muscular tissue. Importantly, despite premature quenching, this work presents the first optical imaging approach to visually mapping the complete chronological breakdown of the scaffold's peripheral boundary layer <i>in vivo</i>, proving that outer functionalized layers eroded prior to internal silk cores. Furthermore, our GPR framework offers a promising approach to address the perennial technical barrier of tissue-mesh overlapping. By mathematically decoupling intrinsic polymer degradation from confounding tissue ingrowth, this model successfully achieved a prediction of the bare scaffold's long-term structural fate in a non-adhered state, providing a preliminary digital twin methodology for lifetime predictions of degradable biomaterials.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"4903-4914"},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Progress on rotator cuff tendon-to-bone interface tissue regeneration and repair.","authors":"Liufang Wu, Changning Qian, Nuanyang Wu, Yinan Shen, Chengzhong Xu, Qingkun Wang, Honghao Hou","doi":"10.1039/d6bm00763e","DOIUrl":"10.1039/d6bm00763e","url":null,"abstract":"<p><p>Tendon-bone interface (TBI) injuries, typified by rotator cuff tears, are common musculoskeletal disorders. Their intrinsic healing capacity is limited by pathological conditions such as local hypoxia, oxidative stress, and secondary fatty infiltration, which prevent spontaneous restoration of the native four-zone gradient architecture. As a result, functional tissue is often replaced by fibrovascular scar tissue with inferior mechanical properties. Because surgical repair alone cannot precisely recreate this complex interface, highly biomimetic tissue-engineered regenerative strategies have emerged as a promising alternative. Beginning with the anatomy of the rotator cuff and the key challenges in treating rotator cuff injuries, this review summarizes the spatiotemporal complexity, physiological vulnerability, and rehabilitation challenges of the TBI. It further discusses the structural composition, fabrication methods, mechanisms of action, and clinical applications of tissue-engineered strategies for TBI regeneration. These approaches use scaffolds based on hydrogels, decellularized matrices, polymers, collagen, and nanoparticles, which can be functionally engineered through graded architectures, aligned structures, mineralization cues, and tailored interfacial properties. In parallel, active components such as stem cells, exosomes, and bioactive factors can be incorporated to recreate a three-dimensional microenvironment that supports tissue regeneration, attenuates inflammation, regulates bone metabolic homeostasis, and promotes vascular regeneration. Although substantial progress has been made in tissue-engineered repair of rotator cuff injuries, future studies should place greater emphasis on digitally enabled and coordinated scaffold design, more robust safety assessment, and quantitative evaluation of therapeutic efficacy. Mechanistic studies and translational research will also be essential to bridge the gap between basic research and clinical application.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":"4811-4845"},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sulagna Dutta, Tridib Banerjee, Arindom Halder, Moupriya Mukherjee, Krishnendu Manna, Goutam Pramanik, Kamalika Sen, Arghya Adhikary, Goutam Ghosh, Ujjal Das
{"title":"Harnessing (-)-epigallocatechin-3-gallate (EGCG) with chitosan-coated liposomes to modulate the radiation effect in cancer cells through alteration in the miR-139-5p-β-catenin axis.","authors":"Sulagna Dutta, Tridib Banerjee, Arindom Halder, Moupriya Mukherjee, Krishnendu Manna, Goutam Pramanik, Kamalika Sen, Arghya Adhikary, Goutam Ghosh, Ujjal Das","doi":"10.1039/d6bm00597g","DOIUrl":"10.1039/d6bm00597g","url":null,"abstract":"<p><p>The development of radio-resistance during radiotherapy represents a significant obstacle in cancer treatment, often resulting in recurrence and mortality. Evidence suggests that the modulations of certain signaling pathways are primarily responsible for the emergence of radio-resistance in tumour cells, and blocking these signaling pathways during radiation therapy may reduce the likelihood of radioresistance development while enhancing radiosensitivity. In this study, chitosan-coated liposomes loaded with EGCG (CHCL EGCG) were used to increase the radiosensitivity of cancer cells. This approach facilitated the sustained release of EGCG, improved bioavailability, and enhanced efficacy relative to free EGCG, and liposome-coated EGCG in HepG2, A549, and MCF7 cell lines. The chitosan component aids in the selective binding of the nanocomposite to the cancer cells. The results also indicated that the suppression of Wnt-β-catenin-stemness-EMT-proliferation axis played a significant role in the development of radiation-sensitivity in cancer cells. RNA sequencing analysis from the GEO database of the radio-resistant MDA-MB-231 cell line and patient samples further confirmed the role of Wnt-β-catenin signaling in the development of radioresistance. Overexpression of β-catenin reversed the effect of CHCL EGCG treatment. Notably, CHCL EGCG increased H3K4me3 levels within the promoter region (intron of the <i>Pdea2</i> gene) of miR-139-5p, thereby elevating its expression in cancer cells. The miR-139-5p levels were already elevated in normal cells due to higher H3K4me3 marks within the promoter region, and CHCL EGCG treatment did not increase H3K4me3 marks further. Therefore, this study perhaps potentially highlights a selective mechanism for enhancing the radiation effect in cancer cells without adversely affecting the normal cells.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}