Materials Today Bio最新文献

{"title":"Strontium-luteolin nanoparticles promote M2 macrophage polarization and accelerate acute wound healing via immune microenvironment regulation","authors":"Xiaowen Zheng ,&nbsp;Wenqi Wang ,&nbsp;Xiaolong Wei ,&nbsp;Jianguo Niu ,&nbsp;Wei Zhang ,&nbsp;Zhenxun Lin ,&nbsp;Wei Wei ,&nbsp;Shipeng Ning ,&nbsp;Min Wang ,&nbsp;Xianwen Wang ,&nbsp;Qingjun Wei","doi":"10.1016/j.mtbio.2026.102873","DOIUrl":"10.1016/j.mtbio.2026.102873","url":null,"abstract":"<div><div>Precise spatiotemporal control of inflammation serves as an effective means to regulate the inflammatory microenvironment and promote wound healing. This study constructed strontium‒luteolin (Sr‒Lut) nanoparticles with a spherical morphology, which demonstrated outstanding radical scavenging capacity through synergistic metal‒ligand effects. Specifically, Sr-Lut efficiently scavenges reactive oxygen species, inhibits the TNF-α/NF-κB and JAK-STAT signaling pathways, promotes M2 polarization, and simultaneously reduces the proinflammatory factor IL-1β and increases the anti-inflammatory factor IL-10. Transcriptomic analysis revealed that Sr-Lut reprogrammed macrophages to downregulate Ccl4 and Retnlg while upregulating extracellular matrix remodeling-associated genes. <em>In vivo</em> experiments demonstrated that Sr-Lut accelerated wound closure in a dose-dependent manner, achieving a healing rate of 94.33 % by day 11, which was significantly greater than the 58.54 % reported in the control group, while also enhancing re-epithelialization and collagen deposition. Wound tissue RNA sequencing revealed that Sr-Lut inhibits the IL-17, Toll-like receptor and NF-κB signaling pathways while promoting the expression of genes associated with epidermal structural components. In summary, a dual-function nanocomposite with both anti-inflammatory and tissue-repair capabilities has been developed, offering a promising immunomodulatory strategy for wound treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102873"},"PeriodicalIF":10.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170458","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":"3D-printed titanium scaffolds coated with a multifunctional photothermal-responsive hydrogel promote osteoporotic bone defect repair","authors":"Chenchen Wang ,&nbsp;Yuan Wang ,&nbsp;Xiaojun Li ,&nbsp;Hao Cao ,&nbsp;Chenfeng Wang ,&nbsp;Sheng Han ,&nbsp;Haotian Chen ,&nbsp;Xin Zhao ,&nbsp;Shude Yang","doi":"10.1016/j.mtbio.2026.102879","DOIUrl":"10.1016/j.mtbio.2026.102879","url":null,"abstract":"<div><div>Osteoporotic bone defects are difficult to repair since conventional titanium scaffolds lack bioactivity and cannot overcome impaired osteogenesis, chronic inflammation, oxidative stress, and cellular senescence. To address these limitations, a multifunctional tannic acid (TA)-based hydrogel coating was developed for 3D-printed titanium alloy scaffolds. The hydrogel was formed from TA, acrylamide, and 3-acrylamidophenylboronic acid, with osteogenic growth peptide (OGP) as a bioactive component. Prussian blue (PB) nanoparticles and quercetin (QUE) were incorporated to provide dynamic crosslinking, photothermal conversion, antioxidant, and anti-inflammatory functions. Stromal cell-derived factor-1α (SDF-1α) was further integrated to recruit endogenous stem cells. The coating exhibited enhanced antiwear and self-healing properties, while near-infrared irradiation (NIR) triggered PB-mediated photothermal effects, thereby improving biotribological performance and accelerating self-repair. <em>In vitro</em>, the hydrogel coating combined with NIR promoted bone marrow mesenchymal stem cell migration, adhesion, and osteogenic differentiation, while simultaneously scavenging reactive oxygen species, attenuating inflammation, reducing cellular senescence, and inducing M2 macrophage polarization. <em>In vivo</em>, the hydrogel coated 3D-printed titanium scaffold markedly enhanced osteoporotic bone defect repair. Overall, this multifunctional hydrogel coating transforms passive titanium scaffolds into bioactive implants, offering a promising strategy for promoting osteoporotic bone regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102879"},"PeriodicalIF":10.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170524","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":"Radioprotectant-loaded visualizable cationic radioactive microspheres: Reduced hepatic tissue damage and intra/postoperative imaging during TARE","authors":"Xun-Zheng Su ,&nbsp;En-Qi Qiao ,&nbsp;Wen-Yu Wu ,&nbsp;Yue-Ran Chen ,&nbsp;Yan Li ,&nbsp;Jin-Hua Song ,&nbsp;Xue-Hao Wang ,&nbsp;Guo-Qiang Shao ,&nbsp;Gao-Jun Teng ,&nbsp;Fei Xiong","doi":"10.1016/j.mtbio.2026.102834","DOIUrl":"10.1016/j.mtbio.2026.102834","url":null,"abstract":"<div><div>Embolization is an effective treatment modality for intermediate- and advanced-stage Hepatocellular carcinoma (HCC). Transarterial radioembolization (TARE), which combines radiotherapy with embolization, not only induces tumor necrosis by occluding blood flow with embolic agents but also exerts local radiotherapeutic effects to damage tumor cells, thereby significantly enhancing the therapeutic efficacy of embolization. Current radiolabeled microspheres used for internal irradiation therapy in HCC have limitations, such as suboptimal embolization efficacy, a tendency for non-target embolization, an inability to track embolic agents during and after surgery, and the generation of reactive oxygen species (ROS) during radiotherapy, which can damage normal tissues. To address these issues, visualizable cationic quaternary ammonium salt-based drug-eluting microspheres capable of loading ¹³¹I and the radioprotective agent amifostine were developed. The microspheres exhibit good embolic properties and can be visualized over an extended period using CT and DSA. The microspheres, carrying a positive charge, are capable of loading amifostine via ion exchange. After loading amifostine, these microspheres can not only provide local radiotherapy within the tumor but also continuously release amifostine locally to neutralize ROS in normal liver tissue. This approach not only enhances the utilization of amifostine in vivo but also protects the liver without compromising the efficacy of TARE thereby further improving the precision of radiotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102834"},"PeriodicalIF":10.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165333","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":"Atomically preserved MXene quantum dots as a redox-responsive nanoplatform for light-controlled bidirectional ROS engineering","authors":"Dejia Hu ,&nbsp;Tianhao Xia ,&nbsp;Danyang Xiao ,&nbsp;Bufeng Liang ,&nbsp;Yuyi Li ,&nbsp;Jinkun Li ,&nbsp;Zhongliao Zeng ,&nbsp;Jianxiong Ma ,&nbsp;Yan Li","doi":"10.1016/j.mtbio.2026.102864","DOIUrl":"10.1016/j.mtbio.2026.102864","url":null,"abstract":"<div><div>MXene quantum dots (MQDs) combine the intrinsic reductive properties of MXenes with the photoactivity induced by quantum confinement, positioning them as promising agents for dynamic redox regulation in therapeutic applications. However, their translation into practice has been limited by persistent synthetic issues, including transition-metal leaching and oxidative degradation. To address these challenges, a sodium ascorbate-mediated coordination and reduction strategy was developed for hydrothermal synthesis of structurally intact Ti₂C MQDs with improved crystallinity and high titanium retention. The resulting MQDs exhibit a unique extension of optical absorption into the visible range, which facilitates efficient ROS generation under visible-light irradiation and confers potent antibacterial properties against pathogenic bacteria. Concurrently, the MQDs demonstrate broad-spectrum ROS scavenging ability. At the cellular level, they effectively reduced oxidative stress and inflammation while promoting M2 macrophage polarization. Capitalizing on these dual redox activities and excellent biocompatibility, a collagen–alginate microneedle patch (MQDs@Col-SA MN) was designed to evaluate their therapeutic potential. In a diabetic wound model, this system achieved ∼80 % smaller wound area than untreated controls at Day 10, while also outperforming a positive control dressing. This study represents the first report of structurally preserved MQDs capable of adaptive redox regulation, underscoring their utility as a versatile platform for microenvironment modulation and regenerative medicine.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102864"},"PeriodicalIF":10.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166038","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 synergistic strategy of AIE and electron asymmetry anchored in covalent organic frameworks for enhanced periodontitis photodynamic therapy","authors":"Xiaofei Zheng ,&nbsp;Tiaotiao Zhu ,&nbsp;Xuanyu Lin ,&nbsp;Pengjing Chen ,&nbsp;Baiwei Ma ,&nbsp;Juanfang Zhu","doi":"10.1016/j.mtbio.2026.102850","DOIUrl":"10.1016/j.mtbio.2026.102850","url":null,"abstract":"<div><div>Periodontitis, a widespread inflammatory disease, is difficult to treat effectively due to incomplete mechanical cleaning and increasing antibiotic resistance. To overcome this issue, we developed a new covalent organic framework, THP-PE-COF, which combines aggregation-induced emission (AIE) with local asymmetric electron distribution (LAED) to enhance photodynamic therapy (PDT). The AIE unit prolongs fluorescence lifetime and inhibits charge recombination, while the electron-donating triphenylthiophene (THP) induces LAED to form local dipoles that promote oxygen adsorption and charge separation. Compared with control THP-PB-COF and THP-BPE-COF, THP-PE-COF exhibited improved light absorption, charge dynamics, and reactive oxygen species (ROS) generation. It showed strong antibacterial activity against <em>Porphyromonas gingivalis</em> and <em>Fusobacterium nucleatum in vitro</em> and demonstrated effective periodontitis treatment with decreased inflammatory responses <em>in vivo</em>. This work pioneered the integration of AIE and LAED in COFs, providing a promising antibiotic-free strategy for periodontal therapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102850"},"PeriodicalIF":10.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166051","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 alginate composite hydrogel with spatiotemporal codelivery of pro-angiogenic and anti-fibrotic agents for synergistic myocardial repair","authors":"Yujuan Jia ,&nbsp;Tongtong Yin ,&nbsp;Zhu Wang ,&nbsp;Lei Chen ,&nbsp;Hongyou Fan ,&nbsp;Jiangbin Wu ,&nbsp;Qian Yu ,&nbsp;Yanxia Zhang ,&nbsp;Zhenya Shen","doi":"10.1016/j.mtbio.2026.102854","DOIUrl":"10.1016/j.mtbio.2026.102854","url":null,"abstract":"<div><div>Myocardial infarction (MI), a leading cause of heart failure, involves dynamic pathological progression from acute ischemia to maladaptive fibrosis. To address this complexity, we engineered an injectable alginate composite hydrogel enabling spatiotemporal codelivery of dual therapeutics targeting distinct MI phases. The system incorporates: (i) UCL-TRO-1938, a newly identified PI3Kα activator promoting angiogenesis via PI3K/Akt signaling, released immediately during the acute injury phase; and (ii) engineered mesoporous silica nanoparticles encapsulating bone morphogenetic protein-9 (BMP-9); these nanoparticles feature an epigallocatechin gallate/zinc ion complex coating enabling pH-responsive payload release specifically within acidic infarct microenvironments. This design aims to align the release of UCL-TRO-1938 with the early demands of angiogenesis and delay BMP-9 release to coincide with the later phase of fibrosis progression. Comparative studies in murine myocardial infarction models showed that this dual-delivery platform resulted in improved outcomes compared with single-agent therapies. Intramyocardial administration significantly reduced apoptosis, enhanced angiogenesis, attenuated fibrosis, and improved cardiac function relative to controls. By synchronizing material properties with stage-specific biological responses, this temporally programmed strategy, which aligns with the pathological progression of MI, achieves enhanced functional recovery compared to conventional monotherapies, providing a clinically viable approach for myocardial repair.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102854"},"PeriodicalIF":10.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165982","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":"Orchestrating the immuno-chondrogenic microenvironment via a bio-inorganic hybrid microsphere system for tendon-to-bone healing","authors":"Wencai Liu ,&nbsp;Yuhao Yu ,&nbsp;Hui Xu ,&nbsp;Weiming Lin,&nbsp;Xin Wang,&nbsp;Yiming Li,&nbsp;Xiping Jiang,&nbsp;Chenrui Yuan,&nbsp;Yifei Wang,&nbsp;Xinyue Yang,&nbsp;Di Wu,&nbsp;Lingzhi Kong,&nbsp;Weilin Yu,&nbsp;Wei Song,&nbsp;Yaohua He","doi":"10.1016/j.mtbio.2026.102851","DOIUrl":"10.1016/j.mtbio.2026.102851","url":null,"abstract":"<div><div>The structural failure of rotator cuff repair is largely attributed to fibrovascular scar formation driven by a persistent inflammatory microenvironment and insufficient fibrocartilage regeneration at the tendon-to-bone interface. To address this, a microfluidic-generated GelMA microsphere system co-encapsulating Zeolitic Imidazolate Framework-8 (ZIF-8) nanoparticles and bone marrow mesenchymal stem cell (BMSC)-derived small extracellular vesicles (sEVs) is developed. This composite system (ZIF-8/sEVs@MS) enables the sustained release of Zn²⁺ and sEVs, which synergistically reprogram macrophages (Mφ) from a pro-inflammatory M1 phenotype to a reparative M2 state and restore the CXCL12/CXCR4 axis for endogenous stem cell recruitment. Transcriptomic analysis elucidates that the system reactivates the PI3K/AKT signaling pathway, thereby reversing inflammation-mediated inhibition and driving chondrogenic differentiation. In a rat rotator cuff repair model, the functionalized microspheres significantly enhance fibrocartilaginous enthesis regeneration, biomechanical structural integrity, and limb function. This study establishes a dual-functional “immuno-chondrogenic” strategy that coordinates immune microenvironment modulation with tissue-specific differentiation to facilitate functional tendon-to-bone healing.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102851"},"PeriodicalIF":10.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165326","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":"NIR-II imaging-guided nanoplatform for synergistic mitochondria-targeted pyroptosis and macrophage reprogramming immunotherapy","authors":"Di Zhang ,&nbsp;Xu He ,&nbsp;Kannappan Vinodh ,&nbsp;Zhehan Yao ,&nbsp;Wanyu Wei ,&nbsp;Jingxiang Liang ,&nbsp;Ningbo Li ,&nbsp;Zhifang Wu ,&nbsp;Sijin Li","doi":"10.1016/j.mtbio.2026.102860","DOIUrl":"10.1016/j.mtbio.2026.102860","url":null,"abstract":"<div><div>Cancer immunotherapy has revolutionized modern oncology by mobilizing the body’s immune system, yet its efficacy remains severely limited in immunologically “cold” tumors, which are defined by poor immune infiltration and low tumor immunogenicity. Here, we report a multi-functional nanoplatform that integrates a new second near-infrared (NIR-II) aggregation-induced emission luminogen (AIEgen), a mitochondria-targeted lonidamine prodrug, and cryo-shocked M1 macrophage membranes (CSMs) to achieve synergistic tumor microenvironment (TME) reprogramming and precision image-guided immunotherapy. The bright NIR-II AIEgen enables high-resolution fluorescence and photoacoustic imaging for real-time tumor visualization and photothermal therapy. The prodrug LND-1-PEG-24, cleavable by TME-overexpressed cathepsin B, preferentially accumulates in mitochondria to trigger caspase-3/GSDME-mediated pyroptosis, leading to the release of danger-associated molecular patterns that markedly enhance tumor immunogenicity. Simultaneously, CSMs promote durable polarization of tumor-associated macrophages (TAMs) toward the tumoricidal M1 phenotype via the TLR2/MAPK pathway, thereby alleviating TME immunosuppression. In tumor-bearing mice, this nanoplatform synergistically enhances cytotoxic T cell infiltration, reverses immune suppression, and effectively inhibits both primary tumor growth and metastatic progression through the activation of systemic antitumor immunity. This work establishes a versatile strategy that unifies NIR-II phototheranostics, mitochondria-targeting pyroptosis, and TAM reprogramming, providing a robust and targeted approach for cancer immunotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102860"},"PeriodicalIF":10.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079672","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":"Graphene oxide coating on two-dimensional glass substrates and three-dimensional zirconia scaffolds for bone tissue regeneration","authors":"Ke Liu ,&nbsp;Yingnan Tian ,&nbsp;Rui Mu ,&nbsp;Xuwen Wang ,&nbsp;Mingzhe Xin ,&nbsp;Haonan Ding ,&nbsp;Yuxin Qian ,&nbsp;Zelong Hu ,&nbsp;Chenyu Zeng ,&nbsp;Xiaocui Wei ,&nbsp;Yi Shuai ,&nbsp;Lei Jin","doi":"10.1016/j.mtbio.2026.102852","DOIUrl":"10.1016/j.mtbio.2026.102852","url":null,"abstract":"<div><div>Zirconia (ZrO₂) scaffolds are considered promising candidates for bone regeneration owing to their excellent biocompatibility and mechanical strength. However, intrinsic bioinertness and the formation of microcracks during sintering remain major challenges that limit their clinical translation. Graphene oxide (GO), characterized by its abundant functional groups and outstanding mechanical properties, has emerged as a valuable material in tissue engineering applications. To address these issues, a silane-mediated dip-coating strategy was employed to deposit GO onto both two-dimensional glass substrates and three-dimensional (3D) ZrO₂ scaffolds, resulting in the design and fabrication of a novel 3D porous GO-ZrO₂ composite scaffold. The GO-coated glass substrates and GO-ZrO₂ scaffolds were comprehensively characterized using multiple analytical techniques. The biocompatible and osteogenic abilities of human dental pulp stem cells (hDPSCs) seeded onto the scaffolds were assessed <em>in vitro</em>. Furthermore, the bone regeneration performance of the GO-ZrO₂ scaffolds were evaluated in a rat calvarial critical-sized defect model. The results demonstrated that the GO layer was uniformly coated on the ZrO₂ scaffolds through covalent bonding (C-O-Si and Si-O-Zr) which effectively bridged microcracks and inhibited their further propagation. Compared with the uncoated ZrO₂ scaffolds, the GO-ZrO₂ scaffolds exhibited increased compressive strength (1.27 ± 0.09 MPa) and elastic modulus (10.71 ± 1.20 MPa). The degradation rate of the GO-ZrO₂ samples was minimal, with only a 0.54 % loss of their initial weight after 3 weeks, and no signs of pH reduction or obvious structural changes. Notably, the incorporation of GO, with its abundant oxygen-containing functional groups, significantly promoted cell adhesion, proliferation, and osteogenic differentiation of hDPSCs <em>in vitro</em>. Mineral deposition was markedly improved, as reflected in an increased calcium-to-phosphorus (Ca/P) atomic ratio (1.21 ± 0.03). Additionally, after an 8-week healing period <em>in vivo</em>, the GO-ZrO₂ scaffolds demonstrated robust new bone formation. Collectively, these findings indicate that the GO-ZrO₂ composite scaffolds represent a highly promising strategy for promoting bone regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102852"},"PeriodicalIF":10.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166049","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":"Ultrasound-triggered carrier-free nanoprodrugs activate cGAS-STING pathway to enhance tumor-targeting chemo-immunotherapy","authors":"Xiaodan Xu ,&nbsp;Peile Jin ,&nbsp;Yijie Chen ,&nbsp;Bihan Wu ,&nbsp;Xia Fang ,&nbsp;Yue Song ,&nbsp;Jieli Luo ,&nbsp;Guowei Wang ,&nbsp;Pintong Huang","doi":"10.1016/j.mtbio.2026.102858","DOIUrl":"10.1016/j.mtbio.2026.102858","url":null,"abstract":"<div><div>Chemotherapy-induced cell apoptosis results in nuclear damage and the subsequent release of double-stranded DNA (dsDNA) fragments, which can stimulate the cGAS-STING pathway to initiate antitumor immune responses. However, this pathway may be less effective due to nonspecific systemic toxicity caused by chemotherapeutic agents and inefficient dsDNA accumulation. This study aimed to develop an ultrasound (US)-triggered carrier-free nanoprodrug PBSN38-curcumin (PBSN38-CUR), incorporating the sonosensitizer curcumin (CUR) and reactive oxygen species (ROS)-responsive prodrug pinacol boronic ester-conjugated 7-ethyl-10-hydroxycamptothecin (PBSN38). The objective was to enhance tumor-targeted chemo-immunotherapy by amplifying <em>in situ</em> DNA damage signals to activate the cGAS-STING pathway in a microenvironment-independent manner. The biocompatible PBSN38-CUR was characterized by high drug-loading capacity, demonstrating negligible toxicity in normal tissues. PBSN38-CUR generated a significant number of ROS in tumor tissues under US irradiation. The toxic chemotherapeutic SN38 was subsequently activated to induce cellular DNA damage and eradicate solid tumors. Moreover, the released CUR led to increased ROS generation and mitochondrial damage through calcium overload, further promoting dsDNA release in the cytoplasm and amplifying a robust immunological effect by activating the cGAS-STING pathway. As a result, US-activated PBSN38-CUR significantly reduced tumor growth in a triple-negative breast cancer model, preventing lung metastases and enhancing the effectiveness of anti-PD-L1 antibody combination therapy. Overall, this study proposed a spatio-controlled strategy for activating the cGAS-STING pathway by amplifying DNA damage through US-triggered prodrug release, thereby highlighting the significant potential of this strategy for clinical translation in tumor-targeted chemo-immunotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"37 ","pages":"Article 102858"},"PeriodicalIF":10.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170390","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}