Biomaterials最新文献

{"title":"In situ incorporation of boronate into carbonized alginate nanogels for targeted inhibition of triple-negative breast cancer metastasis by inducing cytoskeletal disruption, cell growth arrest, and apoptosis","authors":"Saumyadip Sarkar ,&nbsp;Chen-Yow Wang ,&nbsp;Pang-Hung Hsu ,&nbsp;Binesh Unnikrishnan ,&nbsp;Yu Tang ,&nbsp;Shiow-Yi Chen ,&nbsp;Chin-Jung Lin ,&nbsp;Anisha Anand ,&nbsp;Ren-Hong Shih ,&nbsp;Li Er Hean ,&nbsp;Pin-Yuan Chen ,&nbsp;Ruo-Yi Huang ,&nbsp;C. Perry Chou ,&nbsp;Chih-Ching Huang","doi":"10.1016/j.biomaterials.2025.123500","DOIUrl":"10.1016/j.biomaterials.2025.123500","url":null,"abstract":"<div><div>Metastasis is the primary cause of cancer mortality, and its prevention is particularly challenging due to the complex tumor microenvironment. Carbon nanomaterials are well known to act as drug delivery systems for therapeutics. Nonetheless, their inherent capabilities in combating tumor cells remain underexplored. In this study, we report the synthesis and characterization of novel boronate-incorporated alginate carbon nanogels (Bor/Alg-CNGs) as promising anti-metastatic agents for effectively suppressing migration and invasion of triple-negative breast cancer (TNBC) cells, while triggering cell-cycle arrest. Notably, Bor/Alg-CNGs decreased cell viability of TNBC cells through disorganization of F-actin, a critical factor mediating cellular migration. In an <em>in vivo</em> study, Bor/Alg-CNGs reduced metastatic lung nodules in a tumor-induced mouse model by &gt;85 %, compared to the untreated controls. Transcriptomics and proteomics analyses further validated the <em>in vivo</em> results with an in-depth understanding of the role of Bor/Alg-CNGs in the stress response of reactive oxygen species-induced cells and downregulation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, leading to metabolic breakdown, cell growth arrest, and apoptosis. These findings underscore the potent anti-metastatic properties of Bor/Alg-CNGs based on their multifunctional role in inhibiting cellular mechanisms essential for metastasis. Compared to many existing carbon nanomaterials, Bor/Alg-CNGs offer enhanced specificity and efficiency in targeting metastatic pathways. Their ability to target and disrupt metastatic processes while minimizing side effects holds the potential for development as a new class of anti-metastatic agents in cancer therapy, warranting further mechanistic and clinical investigations to realize their full therapeutic potential.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123500"},"PeriodicalIF":12.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290441","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":"Conjugation of peptides to a dendrimer surface to promote the proliferation and differentiation of human pluripotent stem cells into cardiomyocytes and retinal pigment epithelium","authors":"Tzu-Cheng Sung ,&nbsp;Wen-Hui Chao ,&nbsp;Zeyu Tian ,&nbsp;Jianyang Chen ,&nbsp;Chengyu Jiang ,&nbsp;Jian Gong ,&nbsp;Jiandong Pan ,&nbsp;Ting Wang ,&nbsp;Qing-Dong Ling ,&nbsp;Akon Higuchi","doi":"10.1016/j.biomaterials.2025.123506","DOIUrl":"10.1016/j.biomaterials.2025.123506","url":null,"abstract":"<div><div>Human pluripotent stem cells (hPSCs), of which differentiated cells can be used in cell therapy and regenerative medicine, cannot proliferate on traditional polystyrene surfaces. Instead, hPSCs are typically cultivated on surfaces coated with Matrigel, which includes xeno-containing substances. Hence, it is advisable to employ biomaterials conjugated to synthetic peptides to promote hPSCs proliferation. hPSCs have been successfully cultured for more than 10 passages on surfaces conjugated to specific peptides derived from extracellular matrix (ECM) proteins. However, the concentration of peptide solution needed for conjugation is high (typically &gt;1000 μg/mL). To overcome this limitation, novel cell culture biomaterials using a polyamidoamine (PAMAM) dendrimer-based peptide-conjugated surface, which allow high peptide surface density locally, were developed in this study. We successfully cultured hPSCs on a PAMAM dendrimer surface conjugated to a specific peptide designed on the basis of the laminin β4 chain; this surface was generated with a low concentration of peptide (50 μg/mL) that was on the same order of magnitude as that used to coat the surface with ECM solution (5–10 μg/mL). After long-term (10 passages) cultivation on the peptide-conjugated dendrimer surface, hPSCs exhibited pluripotency and the potential to differentiate into cells from all three germ layers, as well as cardiomyocytes for the treatment of myocardial infarction and retinal pigment epithelial cells for the treatment of retinal pigmentosa disease. 3D peptide conjugation (immobilization) at high density on the surface via the PAMAM dendrimer supports maintenance of hPSC pluripotency via low concentrations of peptides during long-term cultivation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123506"},"PeriodicalIF":12.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a multifunctional, injectable biomaterial using hyaluronan as a bioactive nanocarrier","authors":"Louis S. Paone ,&nbsp;Ying Jin ,&nbsp;Julien Bouyer ,&nbsp;Itzhak Fischer ,&nbsp;Peter A. Galie","doi":"10.1016/j.biomaterials.2025.123505","DOIUrl":"10.1016/j.biomaterials.2025.123505","url":null,"abstract":"<div><div>Hyaluronic acid-based biomaterials provide diverse functionality due to the inclusion of multiple bioactive domains within the glycosaminoglycan molecule. This attribute is particularly promising for regenerative strategies to treat central nervous system injury, which is a complex system that requires combinatorial approaches to address different mechanisms. Here, a small molecule inhibitor of transforming growth factor β (TGF-β) signaling, sb431542, and repulsive guidance molecule A (RGMa) antagonist peptide are conjugated to the same hyaluronan-based nanocarrier to simultaneously address multiple aspects of the injury microenvironment. The modified hyaluronan is paired with a thermo-responsive polymeric hydrogel, poloxamer 407, to create an injectable delivery system. Synthesis, characterization, and validation of the injectable platform demonstrates mechanical properties on par with previous scaffolds used in the central nervous system, physiologically relevant release rates of cargo, and the ability to modulate cellular function in a three-dimensional <em>in vitro</em> model. Proof of concept studies in a cervical-level hemisection spinal cord injury animal model indicate increased infiltration of both host axons and astrocytes within the lesion following delivery of the hydrogel. Additionally, tracing of rubrospinal and reticularmotor tracts across the site of injury eight weeks post-injury suggests improvements in connectivity. Overall, this study establishes the utility of combining different biochemical moieties to build heterofunctional nanocarriers and demonstrates that treatments simultaneously addressing multiple aspects of the injury response have the potential to restore connectivity in the central nervous system.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123505"},"PeriodicalIF":12.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306674","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":"Corrigendum to “Programmed surface platform orchestrates anti-bacterial ability and time-sequential bone healing for implant-associated infection” [Biomaterials 313 (2025) 122772]","authors":"Zhou Yu ,&nbsp;Zhaolong Wang ,&nbsp;Yitong Chen ,&nbsp;Yuchen Wang ,&nbsp;Like Tang ,&nbsp;Yue Xi ,&nbsp;Kaichen Lai ,&nbsp;Qi Zhang ,&nbsp;Shuangyang Li ,&nbsp;Danyu Xu ,&nbsp;Anrong Tian ,&nbsp;Mengjie Wu ,&nbsp;Ying Wang ,&nbsp;Guoli Yang ,&nbsp;Changyou Gao ,&nbsp;Tingben Huang","doi":"10.1016/j.biomaterials.2025.123498","DOIUrl":"10.1016/j.biomaterials.2025.123498","url":null,"abstract":"","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123498"},"PeriodicalIF":12.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293041","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-coated NIR light-photodegradable carbon nitride-based gene vectors for gas-gene therapy of liver fibrosis","authors":"Ming-Xuan Liu ,&nbsp;Ya-Qi Zhu ,&nbsp;Yue Yang ,&nbsp;Su-Yun Zhang ,&nbsp;Meng-Zhu Zhou ,&nbsp;Wei Wu ,&nbsp;Yi-Tong Tao ,&nbsp;Yong-Hong Liu ,&nbsp;Yuan Yang ,&nbsp;Xiao-Ling Zhang","doi":"10.1016/j.biomaterials.2025.123503","DOIUrl":"10.1016/j.biomaterials.2025.123503","url":null,"abstract":"<div><div>Hepatic fibrosis impacts millions of patients globally suffering from various liver diseases. Therefore, development of novel therapeutic strategies is urgently required. Since macrophage recruitment increases during liver fibrosis progression, macrophage membrane-coated biomimetic complexes can be designed for targeted anti-liver fibrosis therapy. In this study, a biomimetic “gas-gene” strategy was proposed to enhance anti-liver fibrosis efficacy. A macrophage membrane-coated carbon nitride-based biomimetic delivery platform loaded with DNA nanoparticles (M-PEISeCCNs@DNA) was developed. The macrophage membrane coating facilitated the delivery of M-PEISeCCNs@SBP1 to the liver fibrosis site and reversed the positive charge of the carriers to avoid cation-induced cytotoxicity. Under near-infrared (NIR) irradiation, M-PEISeCCNs@SBP1 could trigger water splitting to produce O₂, thereby mitigating hypoxia and alleviating liver fibrosis. The light-responsive release of the SBP1-DNA plasmid was also achieved through carrier photolysis. The delivered SBP1-DNA and the Se element within the vectors synergistically upregulated the expression of selenium-binding protein-1 (SBP1). Additionally, we demonstrated for the first time that SBP1 is an effective therapeutic target for liver fibrosis, and its overexpression inhibits epithelial-mesenchymal transition (EMT) and attenuates CCl₄-induced liver fibrosis in mice. In this experiment, M-PEISeCCNs@SBP1 effectively treated liver fibrosis in mice through the SBP1-mediated NOTCH2/Wnt pathway.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123503"},"PeriodicalIF":12.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270978","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":"Extracellular matrix glycation epigenetically regulates brain aging and neurodegeneration in the in vitro aged neurovascular model","authors":"Minjeong Jang ,&nbsp;Hae-June Lee ,&nbsp;Eun U Seo ,&nbsp;Hong Nam Kim","doi":"10.1016/j.biomaterials.2025.123504","DOIUrl":"10.1016/j.biomaterials.2025.123504","url":null,"abstract":"<div><div>As life expectancy continues to rise, addressing aging and age-related diseases becomes crucial for maintaining a healthy lifestyle. Advanced glycation end-products (AGEs) accumulate in brain tissue as we age, co-localizing with amyloid β and tau in the brains of elderly and Alzheimer's disease patients. However, the link between increased AGE levels, aging, and neurodegeneration remains unclear. To explore the effect and mechanism of AGEs on the brain, we developed a neurovascular (NV) model that reflects features of an aged brain by integrating an AGE-anchored matrix. Under AGE-incorporated conditions, we observed brain endothelial dysfunction and microglial activation, leading to increased neuroinflammation and neurodegeneration. Notably, we discovered that targeting AGE and its receptor could attenuate AGE-mediated neurodysfunction through the histone-modifying enzyme, KMT2A, in neurons within an aged NV model. Our findings in the NV model align with those observed in aged and Alzheimer's disease mouse models. This aged brain model offers a valuable platform for elucidating the epigenetic mechanisms of brain aging and provides insights into novel anti-aging strategies for age-associated brain disorders.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123504"},"PeriodicalIF":12.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322599","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 controllable self-amplifying oxidative stress strategy for boosting noninvasive sonodynamic therapy and synergistic immunotherapy","authors":"Mingting Zhu,&nbsp;Jiacheng Liu,&nbsp;Yan Li,&nbsp;Zhen Ya,&nbsp;Meiling Liang,&nbsp;Lei Zhang,&nbsp;Yujin Zong,&nbsp;Mingxi Wan","doi":"10.1016/j.biomaterials.2025.123499","DOIUrl":"10.1016/j.biomaterials.2025.123499","url":null,"abstract":"<div><div>The combined application of sonodynamic therapy (SDT) and immune checkpoint blockade may be hindered by the antioxidant defense mechanisms of tumor cells and the immunosuppressive tumor microenvironment (TME). SDT may be enhanced through nanotechnology to improve sonosensitizer delivery and drug release triggered by reactive oxygen species (ROS). However, strategies to amplify ROS cascades and synergize with immune checkpoint blockade remain underexplored. In this study, a pH/ROS dual-responsive nanoplatform (designated as FHPCL NPs) that targets tumor tissues with a “self-amplifying oxidative stress” strategy to synergistically enhance the efficacy of SDT and immunotherapy was developed. This nanoplatform established a “drug release-ROS generation-carrier disintegration” positive feedback loop in the tumor tissues when combined with ultrasound technology, thereby inducing massive ROS production. In a 4T1 breast cancer model, this strategy achieved an in situ tumor suppression rate exceeding 80 %. Importantly, the integrated platform significantly promotes dendritic cell maturation and cytotoxic T lymphocytes infiltration by inducing immunogenic cell death, thereby activating enhanced immune responses and systemic immunological effects. Furthermore, we demonstrated that combining FHPCL NPs-augmented SDT with anti-programmed death ligand 1 markedly inhibited tumor growth and pulmonary metastasis, and established durable immune memory. This study provides a promising strategy for tumor therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123499"},"PeriodicalIF":12.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312694","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":"Emodin-derived red-emissive carbon dots: Light-driven ROS generation and antioxidant activities in non-illuminative regimes","authors":"Shichao Jiang ,&nbsp;Borui Su ,&nbsp;Gaowei Li ,&nbsp;Xiaoyin Liu ,&nbsp;Peng Liu ,&nbsp;Mei Yang ,&nbsp;Jiamei Xiao ,&nbsp;Xingchen Huang ,&nbsp;Dan Wei ,&nbsp;Jing Sun ,&nbsp;Jie Ding ,&nbsp;Chengheng Wu ,&nbsp;Hongsong Fan","doi":"10.1016/j.biomaterials.2025.123496","DOIUrl":"10.1016/j.biomaterials.2025.123496","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) play dual roles in physiological processes and disease pathogenesis, making their precise regulation crucial for therapeutic applications. Herein, we report the rational design of red-emissive carbon dots (CDs) with light-switchable pro-oxidant/antioxidant bifunctionality for precision nanomedicine. Synthesized from emodin and urea via a solvothermal method, these N-doped CDs exhibit: (1) red emission (&gt;650 nm) with enhanced tissue penetration, (2) efficient type I/II ROS generation under light irradiation, (3) effective ROS scavenging in darkness , and superior water solubility and biocompatibility for in vivo applications. Density functional theory (DFT) calculations confirm that N-doping optimizes the spectral properties of Emo-CDs and promotes the generation of ROS. The unique graphene-like core with abundant surface functional groups enables reversible switching between oxidative and antioxidative states under dark conditions. This work establishes a new paradigm for developing intelligent theranostic agents capable of precise oxidative stress regulation, with promising applications in photodynamic and antioxidant therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123496"},"PeriodicalIF":12.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297973","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":"Modulating tumor acidity with hydroxyethyl starch-based nanoparticles by targeting CA9 to eliminate cancer stem cells and overcome immunosuppression","authors":"Qingyuan Deng ,&nbsp;Ao Hua ,&nbsp;Qingfu Zhao ,&nbsp;Zhijie Zhang ,&nbsp;Tian Yang ,&nbsp;Qiang Wang ,&nbsp;Xiangliang Yang ,&nbsp;Zifu Li","doi":"10.1016/j.biomaterials.2025.123501","DOIUrl":"10.1016/j.biomaterials.2025.123501","url":null,"abstract":"<div><div>The acidic microenvironment in solid tumors, primarily driven by Warburg effect, promotes tumor progression, immune evasion, and resistance to therapy. Cancer stem cells (CSCs), a critical subset within tumor tissues, exacerbate this acidity through overexpression of pH-regulating proteins such as carbonic anhydrase IX (CA9), which plays a pivotal role in maintaining pH homeostasis, contributes to immune suppression, and sustains CSC stemness and proliferation. In this study, we designed CA9 inhibitor (CAi) coupled hydroxyethyl starch-based nanoparticles (CHHD-Cu NPs) that integrate doxorubicin (DOX) mediated chemotherapy with copper ions (Cu²⁺) mediated chemodynamic therapy to target and eliminate CA9-expressing CSCs. Upon administration, CHHD-Cu NPs bind to CA9 and disrupt pH regulation, thereby lowering intracellular pH and raising extracellular pH. This pH modulation enhances intracellular releases of DOX and Cu²⁺ and alleviates extracellular acidity to boost effector T cells infiltration and activity. Our rationally designed CHHD-Cu NPs eliminate CSCs in two ways: firstly, by robust intracellular DOX- and copper-induced cytotoxicity, and secondly, via pH modulation-mediated activation of anti-tumor immunity. Our strategy offers novel approaches for treatment of immunosuppressive solid tumors.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123501"},"PeriodicalIF":12.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290442","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":"Biomimetic nanoplatforms for combined DDR2 inhibition and photothermal therapy in dense breast cancer treatment","authors":"Yan Chen ,&nbsp;Ye Yu ,&nbsp;Yonghao Fan ,&nbsp;Wenyan Lu ,&nbsp;Yunpeng Wei ,&nbsp;Julan Wu ,&nbsp;Banzhan Ruan ,&nbsp;Zhenling Wan ,&nbsp;Yangyang Zhao ,&nbsp;Keping Xie ,&nbsp;Wei Jie ,&nbsp;Shaojiang Zheng","doi":"10.1016/j.biomaterials.2025.123497","DOIUrl":"10.1016/j.biomaterials.2025.123497","url":null,"abstract":"<div><div>Breast cancer treatment remains challenging due to the dense, fibrotic tumor microenvironment (TME), which is dominated by cancer-associated fibroblasts (CAFs), hinders drug delivery and promotes therapy resistance. While photothermal therapy (PTT) can induce localized tumor ablation, its efficacy is often limited by poor nanoparticle penetration and CAF-mediated immune suppression. Here, we developed M@P-WIs, a biomimetic nanoplatform that combines PTT with targeted CAF modulation. Unlike conventional approaches, M@P-WIs co-deliver a photothermal agent (IR-780) and the discoidin domain receptor 2 (DDR2) inhibitor WRG-28, enabling simultaneous tumor cell ablation and stromal remodeling. In preclinical studies, this dual-action strategy significantly suppressed metastasis, induced CAF apoptosis, and dismantled the fibrotic barrier while preventing CAF repopulation. In murine breast cancer models, M@P-WIs achieved complete primary tumor regression and established long-term immunological memory, thereby reducing recurrence and metastasis. Importantly, we have identified a novel resistance mechanism, by which PTT alone triggers residual tumor cells to secrete TGF-β-rich exosomes, promoting fibroblast-to-CAF transformation and excessive ECM deposition. M@P-WIs effectively overcome this resistance mechanism by producing complete CAF depletion alongside tumor ablation. Our findings demonstrate that integrating CAF-targeted stromal modulation with PTT synergistically enhances therapeutic efficacy, offering a promising strategy for treating stroma-rich, aggressive tumors.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123497"},"PeriodicalIF":12.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290440","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}