Theranostics最新文献

{"title":"Nanodelivery of Y-27632 by RGD-modified liposome enhances radioimmunotherapy of hepatocellular carcinoma via tumor microenvironment matrix stiffness reprogramming.","authors":"Yang Shen, Zihui Zheng, Xinyao Hu, Zhuolin Zhou, Yangtao Xu, Siyu Wang, Shuhong Yu, Xiaoqin He, Ximing Xu","doi":"10.7150/thno.114892","DOIUrl":"https://doi.org/10.7150/thno.114892","url":null,"abstract":"<p><p><b>Background:</b> Hepatocellular carcinoma (HCC) causes a significant mortality burden worldwide. Radiotherapy (RT) is the primary locoregional treatment modality for HCC. However, the efficacy of RT in HCC is limited by tumor microenvironment (TME) hypoxia, immunosuppression, and extracellular matrix (ECM) stiffness. <b>Methods:</b> We developed a novel RGD-modified liposomal platform (RGD@LP-Y) that encapsulates the ROCK inhibitor Y-27632 through thin-film hydration. We characterized the RGD@LP-Y by the transmission electron microscope (TEM), UV-Vis spectrophotometer, and dynamic light scattering instrument (DLS). A high-stiffness hydrogel co-culture system mimicking mechanical TME was established to explore the role of RGD@LP-Y on matrix stiffness remodeling. <i>In vitro</i> evaluations included cytotoxicity, reactive oxygen species (ROS) generation, mitochondrial function, immunogenic cell death (ICD) markers, and immune cell activation. Mechanistic investigations encompassed matrix stiffness regulation analysis, flow cytometry profiling of pro-inflammatory macrophages, dendritic cell (DC) maturation, transcriptome sequencing, and western blotting. <i>In vivo</i> validation used xenograft models treated with intravenous RGD@LP-Y and localized RT. Biosafety was confirmed through organ histology, serum biochemistry analysis, and hemolysis assay. <b>Results:</b> RGD@LP-Y downregulated matrix stiffness markers (YAP/COL1) and activated PI3K/AKT/NF-κB signaling to drive pro-inflammatory macrophage polarization and DC maturation. The synergistic effects were observed in combination with RT. The treatment of RGD@LP-Y and RT inhibited HCC proliferation, induced apoptosis, suppressed mitochondrial respiration, elevated intracellular ROS, and thus enhanced ICD. <i>In vivo</i>, RGD@LP-Y+RT demonstrated potent tumor suppression and immune activation without systemic toxicity. <b>Conclusion:</b> RGD@LP-Y enhances RT sensitivity by remodeling ECM stiffness, modulating the hypoxia and immunosuppressive conditions within TME, and enhancing the ICD. The study provides a safe combinatorial approach for HCC therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8569-8586"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic integration of extracellular vesicles and metal-organic frameworks: unlocking new opportunities in disease diagnosis and therapy.","authors":"Peiye Xu, Jiaxuan He, Ting Xu, Weijie Wang, Baihui Wu, Rongbing Chen, Hanbing Wang, Qinsi Yang, Wei Wu, Da Sun","doi":"10.7150/thno.113474","DOIUrl":"https://doi.org/10.7150/thno.113474","url":null,"abstract":"<p><p>The combination of extracellular vesicles (EVs) and metal-organic frameworks (MOFs) is a cutting-edge strategy in nanomedicine, leveraging the immune evasion, targeting capabilities, and biocompatibility of EVs with the high loading capacity and tunable functionality of MOFs. This review comprehensively discusses the latest advancements in the EV-MOF collaborative system, including its combined form and preparation process, focusing on its synergistic applications in disease diagnosis and treatment. EV-MOF platforms have demonstrated enhanced sensitivity in biosensing and bioimaging, offering new avenues for early cancer detection using signal amplification and fluorescence imaging technologies. Therapeutically, EV-MOF systems have demonstrated significant promise in drug delivery, cancer treatment, rheumatoid arthritis, ulcerative colitis, wound healing, bone regeneration, and anti-infection applications, delivering targeted therapies with controlled drug release, and improved biocompatibility. Despite these advancements, challenges remain in optimizing the binding methods between EVs and MOFs, ensuring their stability, and understanding their <i>in vivo</i> mechanisms. Addressing these may be key to unlocking the full clinical potential of EV-MOF systems. This review provides a critical analysis of the current state of research, offering insights and guidance for future exploration in this rapidly evolving field.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8609-8638"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fe-flavonoid nanozyme as dual modulator of oxidative stress and autophagy for acute kidney injury repair.","authors":"Ranran Luo, Zhongsheng Xu, Chenxi Zhang, Zening Zhang, Pengchen Ren, Xiaojing He, Jingjing Zhang, Yun Liu","doi":"10.7150/thno.111874","DOIUrl":"https://doi.org/10.7150/thno.111874","url":null,"abstract":"<p><p><b>Background:</b> Acute kidney injury (AKI), marked by a high mortality rate, remains a significant clinical challenge owing to limited therapeutic options. Oxidative stress is a key driver of AKI pathogenesis, underscoring the urgent need for innovative interventions. Recent advances demonstrate the potential of reshaping the oxidative stress microenvironment and activating intracellular autophagy to facilitate tissue repair. Nanotechnology-based antioxidants are emerging as promising approaches for AKI. Here, we present a novel nanoscale natural antioxidant platform for AKI treatment, incorporating reactive oxygen species (ROS) scavenging, oxidative stress modulation, anti-inflammatory properties and autophagy activation, which leverages these synergistic functions and lays the groundwork for clinical translation of next-generation nanotherapeutics in AKI. <b>Methods:</b> We synthesized a Fe-flavonoid nanozyme (FD@BSA) composed of ferric chloride hexahydrate, dihydromyricetin (DMY), and bovine serum albumin (BSA). FD@BSA integrated DMY's antioxidant and autophagy-activating functions with iron-mediated catalytic activity. Its therapeutic efficacy was evaluated in two oxidative stress-driven renal injury models: H₂O₂-induced ROS overload in human renal proximal tubular epithelial (HK-2) cells and glycerol-mediated AKI mice. Mechanistic studies employed laser confocal microscopy to visualize intracellular ROS scavenging and autophagy activation, while Western blotting and immunohistochemistry assessed protein expression and tissue-level pathology. <b>Results:</b> After intravenous administration, FD@BSA nanozyme selectively accumulated in the kidneys of water-restricted, glycerol-induced AKI mice. <i>In vitro</i> studies demonstrated that FD@BSA significantly decreased ROS accumulation in HK-2 cells, enhanced cell viability, attenuated inflammatory responses, and induced mitophagy, thereby preserving cellular homeostasis and alleviating injury. <i>In vivo</i>, FD@BSA treatment markedly ameliorated glycerol-induced AKI. Mechanistically, this protective effect was mediated by inhibition of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and upregulation of light chain 3 (LC3)-dependent autophagy, which together reduced ROS-driven cellular damage and mitigated renal injury, highlighting FD@BSA as a promising strategy for AKI. <b>Conclusion:</b> This study establishes FD@BSA nanozyme as a versatile nanotherapeutic platform for AKI, which can effectively remodel the oxidative stress microenvironment by scavenging excessive ROS and activating intracellular autophagy. Such multifunctionality extends FD@BSA's applicability beyond AKI to other ROS-driven pathologies, positioning it as a next-generation, nanotechnology-based strategy for the treatment of oxidative stress-related diseases.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8658-8674"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FBLN7 KO attenuates age-related cardiac fibrosis by promoting TGFBR3/ALK1/Smad1 signaling and inhibiting the profibrotic phenotypes of cardiac fibroblasts.","authors":"Xuehui Zheng, Guoqing Yao, Huaitao Yu, Binghui Kong, Yuan Zhao, Yang Hu, Xiangping Ma, Jinghan Hai, Panpan Xu, Yun Ti, Peili Bu","doi":"10.7150/thno.116477","DOIUrl":"https://doi.org/10.7150/thno.116477","url":null,"abstract":"<p><p><b>Rationale:</b> Aging induces structural and functional changes in the heart, including left ventricular (LV) hypertrophy, a decline in diastolic function, and even heart failure. Fibulin 7 (FBLN7) is a key mediator of extracellular matrix (ECM) remodeling under pathological conditions. In our study, we aim to explore whether FBLN7 is also involved in the development of age-related cardiac fibrosis and its underlying mechanisms. <b>Methods:</b> We generated naturally aged FBLN7 knockout and wild-type mice (18 months old). Western blot and immunofluorescence assays were employed to investigate the biological function of FBLN7 in senescent cardiac fibroblasts. The interaction between FBLN7 and cell membrane receptors was explored through molecular docking and co-immunoprecipitation techniques. The interaction between FBLN7 and natural products was explored through virtual screening, molecular dynamics simulations and surface plasmon resonance (SPR). <b>Results:</b> Our results demonstrated that the cardioprotective effects observed in aged FBLN7 knockout (KO) mice are mediated by the inhibition of profibrotic phenotypes in senescent cardiac fibroblasts (CFs), which reduces age-related myocardial fibrosis and ultimately improves cardiac diastolic function. The observation that overexpressing FBLN7 in fibroblast-specific protein 1 positive (FSP1⁺) cells of aged mice exacerbates age-related myocardial fibrosis further supports this finding. Mechanistically, we identified that FBLN7 promotes the proliferation, migration, actin remodeling, and collagen production of senescent CFs at least partially by binding to TGFBR3 and reducing its protein levels, thereby inhibiting the activation of the ALK1-Smad1/5/9 pathway. Additionally, we identified a natural product, Ginsenoside Ro, that physically interacts with FBLN7 and validated its antifibrotic activity both in vitro and in vivo. <b>Conclusions:</b> These findings reveal FBLN7 reverses the impaired profibrotic phenotypes of senescent CFs, thereby aggravating age-related cardiac fibrosis. Given that age-related fibrosis is a significant pathological factor in heart failure with preserved ejection fraction (HFpEF), downregulating FBLN7 and/or interfering with its function may represent an effective therapeutic strategy for HFpEF.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8531-8552"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.","authors":"Hanzhe Shi, Mingming Xiao, Yangyi Li, Xiyu Liu, Jintong Na, Chen Liang, Jie Hua, Qingcai Meng, Miaoyan Wei, Wei Wang, Jin Xu, Xianjun Yu, Si Shi","doi":"10.7150/thno.112633","DOIUrl":"https://doi.org/10.7150/thno.112633","url":null,"abstract":"<p><p>Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, the expression of senescence markers, and the acquisition of senescence-associated secretory phenotype (SASP). In this review, we discuss the role of cellular senescence within the tumor microenvironment. Some senescent innate immune cells fail to sustain their antitumor function and may even promote tumor progression. Senescent CD8⁺ and CD4⁺ T cells become dysfunctional and are implicated in immunosuppression, angiogenesis, and resistance to immunotherapy. Research on stromal senescence primarily focuses on the SASP. The SASP functions as a double-edged sword. It promotes immune surveillance in the early stages of a tumor while inhibiting tumor immunity in its advanced stages. Strategies to target senescence in cancer therapies include four main approaches: inducing senescence, inhibiting tumor-promoting SASP, clearing senescent cells, and reversing senescence. Although not yet in clinical practice, these approaches hold promise for future cancer treatments.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8675-8703"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals that myeloid S100A8/A9 is a novel regulator of the transition from adaptive hypertrophy to heart failure after pressure overload.","authors":"Wei-Jia Yu, Wen-Xi Jiang, Shu-Jing Liu, Hui-Hua Li, Qiu-Yue Lin","doi":"10.7150/thno.118369","DOIUrl":"https://doi.org/10.7150/thno.118369","url":null,"abstract":"<p><p><b>Rationale:</b> Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. <b>Methods:</b> Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45⁺ immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an <i>in vitro</i> coculture system. <b>Results:</b> S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2⁺ macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. <b>Conclusion:</b> The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8587-8608"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable hydrogels based on mussel-inspired nanocomposite microspheres for non-compressible intra-abdominal hemorrhage control.","authors":"Tao Liu, Peng Ma, Fengya Jing, Yinghua Tao, Jinfang Lu, Dandan Wei, Liuxin Yang, Feiling Feng, Yonghua Li, Hongbin Yuan, Tianzhu Zhang","doi":"10.7150/thno.118901","DOIUrl":"https://doi.org/10.7150/thno.118901","url":null,"abstract":"<p><p><b>Background:</b> The development of hemostatic materials for non-compressible intra-abdominal hemorrhage in complex pre-hospital emergency settings remains a formidable challenge. <b>Methods:</b> A novel injectable hydrogel based on mussel-inspired nanocomposite microspheres was designed. The biocompatible hydrogel was formed by hydrating gelatin methacryloyl (GelMA) cryogel microspheres-reinforced with polydopamine (PDA)-intercalated nanoclay-with sterile saline, offering the dual benefits of convenient storage of microspheres and precise delivery to deep bleeding points via injection. <b>Results:</b> The cryogel microspheres, featuring rapid water and blood absorption within 1 second, exhibited outstanding procoagulant capabilities in both <i>in vitro</i> and <i>in vivo</i> experiments, showing potential as hemostatic agents for open wounds. Notably, the on-demand formulated hydrogel effectively controlled severe bleeding within 2 minutes post-injection in rat liver volumetric defect and partial resection models, demonstrating ​significantly enhanced applicability compared to ​bulk hemostatic agents for irregular wounds. Additionally, ultrasound-guided application in a porcine liver ​rupture model confirmed that the hydrogel rapidly filled and sealed deep wounds, interacted with blood components to form stable, large clots adhering to the wound surface, and thus established durable hemostasis. <b>Conclusion:</b> This study presents a promising injectable hemostatic material for pre-hospital emergency hemorrhage control.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8509-8530"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosynthetic gas vesicles as a novel ultrasound contrast agent for diagnosing and treating myocardial infarction.","authors":"Zihang Wang, Maierhaba Yibulayin, Kezhi Yu, Tingting Liu, Lina Guan, Baihetiya Tayier, Lingjie Yang, Shangke Chen, Yuming Mu, Fei Yan","doi":"10.7150/thno.118543","DOIUrl":"https://doi.org/10.7150/thno.118543","url":null,"abstract":"<p><p><b>Rationale:</b> Myocardial contrast echocardiography (MCE) plays an important role in diagnosis of myocardial infarction (MI). However, its accuracy is limited by image quality because microbubble-based MCE produces negative contrast enhancement in the infarcted myocardial tissue. This study aimed to develop nanoscale gas vesicles (GVs) from <i>Halobacteria NRC-1</i> (hGVs) and GV-expressing genetically engineered <i>E. coli</i> (eGVs) and compare their imaging performance with commercial Sonovue in MI rats. <b>Methods:</b> We developed nanoscale gas vesicles (GVs) from <i>Halobacteria NRC-1</i> (hGVs) and GV-expressing genetically engineered <i>E. coli</i> (eGVs) and compared their imaging performance with Sonovue in MI rats. Unlike SF₆-filled Sonovue, GVs are air-filled protein nanobubbles with unique shapes. We used immunofluorescence and TEM to examine GVs' distribution in myocardial tissue and analyzed the mechanisms of their penetration into infarcted areas. Additionally, we evaluated the potential of oxygen delivery to ischemic myocardium using ultrasound-targeted bubble destruction. <b>Results:</b> hGVs produced significantly positive contrast enhancement and could last for a longer time in the infarcted area. Immunofluorescence and TEM examination confirmed that hGVs penetrated out the blood vessels into the ischemic myocardium and eGVs primarily retained around endothelial cells, while Sonovue could not pass through the damaged vessels. Mechanistic analysis revealed that inflammatory cytokines results in leaky blood vessels, facilitating the penetration of nanoscale GVs into the infarcted myocardial tissue. Moreover, hGVs exhibited excellent imaging performance across different pathological stages, especially during the inflammatory phase. More importantly, oxygen delivery into the ischemic myocardium through ultrasound-targeted bubble destruction technology greatly promoted the functional recovery of the ischemic myocardium. <b>Conclusions:</b> hGVs demonstrated superior imaging performance and penetration capabilities specifically at the myocardial infarction sites in rats.Their ability to provide positive contrast and deliver oxygen via ultrasound-targeted bubble destruction enables improved diagnosis and treatment of MI.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8553-8568"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic inflammation-induced adipose tissue remodeling drives psoriasis exacerbation in obesity through epigenetic and immunometabolic dysregulation.","authors":"Jinsun Jang, Mijoo Ahn, Jiyeong Jeong, Eun-Hui Lee, Ok-Hee Kim, Seul-A Joo, Seung Eun Baek, Han-Joo Maeng, Yun Hak Kim, In-Sun Hong, Byung-Chul Oh, Ik Soo Kim, Hee Joo Kim, YunJae Jung","doi":"10.7150/thno.116796","DOIUrl":"https://doi.org/10.7150/thno.116796","url":null,"abstract":"<p><p><b>Rationale:</b> Disruption of adipose tissue homeostasis is increasingly recognized as a key driver of psoriatic inflammation in the context of obesity. However, the mechanisms linking adipose dysfunction to disease severity remain incompletely understood. <b>Methods:</b> We employed an obese mouse model of psoriasis induced by topical imiquimod application or dermal IL-23 injection. Inflammatory profiling from these mice was integrated with multi-omic single-nucleus sequencing targeting RNA and chromatin accessibility to investigate genetic and epigenetic alterations in adipose tissue. <b>Results:</b> Obese mice developed markedly aggravated psoriatic dermatitis following imiquimod treatment, accompanied by increased systemic inflammatory responses and a significant reduction in fat mass. Histological and molecular analyses revealed extensive monocyte-macrophage infiltration into perigonadal adipose tissue, increased expression of pro-inflammatory genes, and upregulation of cell death-associated molecules in obese mice relative to lean counterparts. In contrast, IL-23 injection elicited comparable skin inflammation in both lean and obese mice without inducing adipose tissue loss or systemic inflammation. Multi-omic profiling of imiquimod-treated obese mice revealed genetic and epigenetic changes in adipocytes that promote fatty acid consumption. Furthermore, a shift was observed in macrophage populations-from a lipid-associated subset with active intercellular communication in IL-23-treated mice to disorganized macrophage compartments with monocyte accumulation in imiquimod-treated mice. <b>Conclusions:</b> These findings suggest that obesity sensitizes adipose tissue to homeostatic disruption, establishing it as a critical immunometabolic interface that drives psoriasis exacerbation in response to systemic inflammatory cues.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8639-8657"},"PeriodicalIF":13.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitosan activates NLRP3 inflammasome and cGAS-STING to suppress cancer progression through hexokinase 2 dissociation and mitochondrial dysfunction.","authors":"Lu Li, Liting You, Zhenfei Bi, Ziqi Zhang, Binwu Ying, Min Luo, Xiawei Wei","doi":"10.7150/thno.112009","DOIUrl":"https://doi.org/10.7150/thno.112009","url":null,"abstract":"<p><p><b>Background:</b> Chitosan, a natural polysaccharide with known immunostimulatory potential, has shown promise in cancer therapy. However, its direct role in modulating antitumor immunity and the underlying mechanisms remain unclear. This study aimed to explore how unmodified chitosan influences tumor progression and immune responses through innate immune signaling pathways. <b>Methods:</b> Murine tumor models (CT26, B16-F10) were used to evaluate the antitumor effects of chitosan in vivo. Flow cytometry and histological analyses assessed changes in immune cell infiltration. Primary macrophages and gene knockout models were used to investigate the molecular mechanisms, including inflammasome activation, mitochondrial function, and hexokinase 2 (HK2) location, via ELISA, western blotting, mitochondrial assays. <b>Results:</b> Chitosan treatment suppressed tumor growth and metastasis, while promoting infiltration of neutrophils, monocytes, and activated T cells in the tumor microenvironment. Mechanistically, chitosan and its bioactive degradation product, N-acetylglucosamine (NAG), induced the dissociation of HK2 from mitochondria, triggering mitochondrial dysfunction, ROS overproduction, and mtDNA release. These signals jointly activated both the NLRP3 inflammasome and the cGAS-STING pathway. The antitumor effect of chitosan was attenuated in <i>Nlrp3</i> ^-/- and <i>Sting</i> ^-/- mice, confirming the essential roles of both pathways. <b>Conclusions:</b> Chitosan orchestrates dual activation of NLRP3 and cGAS-STING signaling via HK2 dissociation and mitochondrial dysfunction, reprogramming the tumor immune microenvironment and enhancing antitumor immunity. These findings support chitosan's potential as a multifunctional immunoadjuvant for improving immunotherapy in resistant cancers.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 16","pages":"8473-8487"},"PeriodicalIF":13.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}