Theranostics最新文献

{"title":"Optical theranostics in ischemic heart disease: from molecular insights to clinical translation.","authors":"Yangjie Xiao, Jing Zhang, Lu Sun, Ke Wang, Yan Chen, Qiaojin Zheng, Ying Li","doi":"10.7150/thno.114307","DOIUrl":"10.7150/thno.114307","url":null,"abstract":"<p><p>Accurate risk stratification of ischemic heart disease (IHD) remains pivotal for mitigating associated global health burdens. Optical theranostics, combining imaging and therapeutic capabilities through light-based technologies, has emerged as a transformative strategy for IHD management. Advanced modalities mainly including optical coherence tomography, near-infrared fluorescence imaging, and photoacoustic imaging enable high-resolution visualization of coronary anatomy, myocardial perfusion, and molecular biomarkers. These modalities complement traditional cardiovascular imaging by providing real-time functional and molecular data with enhanced spatial resolution. Concurrently, phototherapy strategies such as image-guided photodynamic and photothermal therapies show therapeutic potential in preclinical studies. Integrated theranostic platforms now operationalize closed-loop workflows, where diagnostic imaging directly informs therapeutic parameters and monitors treatment response. While challenges persist in clinical translation-including tissue penetration limitations and safety optimization-ongoing developments in contrast agents, device miniaturization, and multimodal integration are accelerating practical applications. This review examines current progress in optical theranostics for IHD, analyzing technical principles, preclinical/clinical implementations, and translational barriers to optimize cardiovascular care through light-based technologies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"6789-6817"},"PeriodicalIF":12.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529625","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":"X-ray-responsive dissolving microneedles mediate STING pathway activation to potentiate cutaneous melanoma radio-immunotherapy.","authors":"Wen Hu, Xiaohong Hong, Xinyu Zhang, Hongfan Chen, Xin Wen, Feng Lin, Jingwen Liu, Chenfenglin Yang, Binglin Cheng, Hanrui Zhu, Moting Zhang, Ruzhen Chen, Tingting Peng, Xinran Tang","doi":"10.7150/thno.110841","DOIUrl":"10.7150/thno.110841","url":null,"abstract":"<p><p><b>Background:</b> Radiotherapy (RT) often activates the cyclic GMP-AMP synthase (cGAS) stimulator of interferon response cGAMP interactor (STING) signaling pathway and induces systemic immunotherapy effects by triggering immunogenic cell death (ICD) in various solid tumors. However, RT-induced ICD usually falls short in eradicating distant tumors because of moderate anti-tumor immune responses. <b>Methods:</b> In this study, Mn-ZIF-8 nanoparticles and microneedles were prepared, and their physical and chemical properties were characterized. Subsequently, <i>in vitro</i> experiments using B16 and A375 cutaneous melanoma cell lines were conducted to investigate the radiosensitivity characteristics of Mn-ZIF-8 and its mechanism for enhancing RT efficacy. Moreover, mouse models bearing primary and distant B16 cutaneous melanoma were established to clarify the immunomodulatory effect and antitumor efficacy of Mn-ZIF-8 microneedles when combined with RT and immunotherapy. <b>Results:</b> A percutaneous delivery method based on soluble microneedles (MNs) with Mn²⁺-loaded, X-ray-responsive zeolite imidazolate frame-8 (ZIF-8) was designed. This microneedle-based drug delivery system, combined with RT, promoted the radiosensitivity of cutaneous melanoma and reinforces ICD by augmenting STING pathway activation. Furthermore, after X-ray irradiation, Mn-ZIF-8 MNs continuously released Mn²⁺ in the tumor to enhance cGAS-STING activation. This promoted dendritic cell maturation and antigen presentation, and potentiated a T cell mediated immune response. Thus, the local and systemic immune effects induced by RT were amplified when combined with immune checkpoint inhibitors. <b>Conclusion:</b> The microneedle patches with X-ray-responsive, rapid dissolution and controlled release abilities have the potential to enhance the radioimmunotherapy efficacy for cutaneous melanoma.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"6919-6937"},"PeriodicalIF":12.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529562","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":"Bioinspired exosome-SiO₂ nanohybrid therapeutic for rheumatoid arthritis treatment.","authors":"Qicui Zhu, Ruofei Chen, Xueting Wu, Yuanyuan Zhou, Zexin Wang, Huaixuan Zhang, Haofang Zhu, Lingyun Sun, Zongwen Shuai","doi":"10.7150/thno.108296","DOIUrl":"10.7150/thno.108296","url":null,"abstract":"<p><p><b>Objective:</b> Due to their anti-inflammatory and immunomodulatory capabilities, adipose-derived stem cells (ADSC) are currently considered a promising option for the management of rheumatoid arthritis (RA). To tackle the problems of immunogenicity and tumorigenicity linked to the direct use of cells, current research is focused on the development of effective nanomedicines utilizing ADSC-derived exosomes (ADSC-EXO) for cell-free regenerative medicine. <b>Methods:</b> Methotrexate (MTX) was loaded into mesoporous silica through physical adsorption to produce SiO₂-MTX, with subsequent incorporation into ADSC-EXO via ultrasonication to produce AE@SiO₂-MTX. Particle size, surface charge, and stability were characterized using dynamic light scattering (DLS) and zeta potential analysis. <i>In vitro</i>, the effects of the nanomaterials were evaluated by assessing the inverse polarization effect of AE@SiO₂-MTX on RAW264.7 macrophages, as well as on the migration and invasion capabilities of fibroblast-like synovial cells (FLS). <i>In vivo,</i> targeting and therapeutic effects on joint inflammation were examined using adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) mouse models. <b>Results:</b> The AE@SiO₂-MTX demonstrated sustained drug release, high biocompatibility, and rapid cellular internalization. <i>In vitro</i>, the delivery system alleviated chronic inflammation by inducing macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, as well as suppressing FLS migration and invasion. <i>In vivo</i> studies revealed that administration of ADSC-EXO outperformed ADSC transplantation in alleviating RA symptoms. Intravenously delivered AE@SiO₂-MTX exhibited targeted accumulation in inflamed joints, significantly reducing joint swelling, synovial hyperplasia, and bone/cartilage degradation in CIA model mice. <b>Conclusions:</b> The findings show that AE@SiO₂-MTX is a robust cell-free therapeutic platform for RA management. Synergy between the immunomodulatory properties of ADSC-EXO and MTX controlled release, this system can overcome the limitations of conventional cell therapies and achieve targeted anti-inflammatory and tissue-protective effects. This strategy offers a promising translational avenue for RA treatment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6553-6571"},"PeriodicalIF":12.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302865","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":"Activatable biomimetic probe with aggregation-induced emission characteristics for non-invasive monitoring of allograft rejection.","authors":"Mengdan Ding, Fang He, Shuangze Han, Wuqi Zhou, Tian Huang, Nan Cui, Yuanting Quan, Wenqu Li, Wenyuan Wang, Tang Gao, Mingxing Xie, Li Zhang","doi":"10.7150/thno.110866","DOIUrl":"10.7150/thno.110866","url":null,"abstract":"<p><p><b>Abstract</b>: Background: Allograft rejection remains a major barrier to the long-term success of organ transplantation. The current gold standard for diagnosis-tissue biopsy is invasive and carries inherent risks, including sampling errors, procedural complications, and high costs. There is a pressing need for an efficient, non-invasive strategy for the early detection and monitoring of transplant rejection. Methods: We developed a macrophage-targeted, activatable imaging probe (<b>MTBPB/GPs</b>) by encapsulating the H₂O₂-responsive aggregation-induced emission (AIE) molecule <b>MTBPB</b> into glucan particles (GPs) via electrostatic and hydrophobic interactions. The probe's responsiveness to H₂O₂ was characterized using UV-vis and fluorescence spectroscopy. Biocompatibility was evaluated through hemolysis assays, immunogenicity testing, biochemical analysis, and histopathology. Macrophage polarization and probe specificity were assessed using confocal laser scanning microscopy (CLSM), flow cytometry (FCM), and ELISA. A murine dorsal skin transplantation model was established to dynamically monitor graft rejection and the therapeutic efficacy of FK506, using <i>in vivo</i> fluorescence imaging at postoperative days (POD) 1, 3, 5, and 7. Pathological validation was performed via H&E staining and immunofluorescence. Results: <b>MTBPB/GPs</b> exhibited excellent biosafety, with low cytotoxicity, minimal hemolytic activity, low immunogenicity, and negligible organ toxicity. Upon oral administration, the fluorescence signal of <b>MTBPB/GPs</b> was selectively activated by M1 macrophages, enabling early and sensitive detection of transplant rejection. Moreover, a single oral dose allowed real-time tracking of immunosuppressive therapy with FK506<b>.</b> Conclusion: <b>MTBPB/GPs</b> represent a promising non-invasive platform for early diagnosis and longitudinal monitoring of transplant rejection and therapeutic response, with strong translational potential in solid organ transplantation.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6572-6592"},"PeriodicalIF":12.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302852","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":"SUMOylation of SARS-CoV-2 spike protein is a key target for broad-spectrum antiviral therapy.","authors":"Xinyu Wang, Gaowei Hu, Yupeng Shao, Zhongwei Dong, Lina Liu, Yixuan Wang, Yaxi Xie, Nuoya Yu, Caixia Zhu, Fang Wei, Yuping Jia, Yuyan Wang, Qiliang Cai","doi":"10.7150/thno.111256","DOIUrl":"10.7150/thno.111256","url":null,"abstract":"<p><p><b>Background:</b> Dynamic SUMO modifications play crucial roles in orchestrating cellular response to various stimuli, including viral infection, and hold significant therapeutic potential. The Spike (S) protein, a surface glycoprotein of SARS-CoV-2 (a global health threat), serves as the key mediator for viral entry and is a critical target for drug development. However, the function of SUMOylation in the Spike protein remains largely unclear. <b>Methods:</b> The SUMO modification of Spike was assessed by immunoprecipitation (IP), denatured IP and immunoblotting assays in lung epithelial cells or SUMO deficient cell line models. The effect of Spike SUMOylation on viral infection was explored by site-direct mutation, cell-to-cell transmission, cell-free infection, quantitative PCR and immunofluorescence staining experiments. The role of Spike SUMOylation-derived peptides was investigated using viral intranasally infection, immunohistochemistry assay in transgenic mouse model. <b>Results:</b> SARS-CoV-2 infection triggers the relocation of SUMO1 to the cytoplasm and SUMO2 to the perinuclear region. Notably, SUMO1 knockout increases Spike trimer formation and its co-localization with SUMO2 at perinuclear puncta, which facilitates virion particle release. SUMO2 knockout leads to enhanced Spike cleavage and promotes viral cell-to-cell transmission. Further bioinformatic and immuno-precipitation analyses reveal that the Spike protein contains highly conserve SUMO-interacting motifs (SIMs) and selectively promotes either SUMO1 (via SIM1) or SUMO2 (via SIM3/4) modifications on lysine residues 129 and 1269, respectively. Importantly, these modifications can be efficiently disrupted by the SIM2 motif. A cell-penetrating peptide (cpSIM2), derived from the SIM2 motif, exhibits robust and broad-spectrum inhibitory activity against SARS-CoV-2 variants infection <i>in vitro</i> and in hACE2-transgenic mice model. <b>Conclusions:</b> This study uncovers critical features of SUMOylation in regulating Spike-mediated viral spread and pathogenesis, providing a potential broad-spectrum therapeutic target for drug development against emerging SARS-CoV-2 infection.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6369-6386"},"PeriodicalIF":12.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302822","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":"Large-scale super-resolution optoacoustic imaging facilitated by FeNP/ICG-loaded coreless polyelectrolyte microcapsules.","authors":"Daniil Nozdriukhin, Shuxin Lyu, Daniel Razansky, Xosé Luís Deán-Ben","doi":"10.7150/thno.112050","DOIUrl":"10.7150/thno.112050","url":null,"abstract":"<p><p><b>Rationale:</b> Localization optoacoustic tomography (LOT) enhances imaging of deep-tissue microvasculature by leveraging flowing contrast particles. However, achieving high-resolution, large-scale imaging requires contrast agents with strong per-particle signal, good biocompatibility, and prolonged circulation time. This study introduces coreless polyelectrolyte microcapsules (MCs) encapsulating indocyanine green (ICG) and iron oxide nanoparticles (FeNP) to overcome current limitations in LOT imaging. <b>Methods:</b> MCs were engineered using a layer-by-layer technique by depositing polyelectrolytes, FeNP and ICG on a CaCO₃ core, which was eventually dissolved. Their optical, morphological, and biocompatibility properties were characterized via UV-Vis-NIR spectroscopy, SEM, and toxicity assays <i>In vitro</i> and <i>In vivo</i>. Optoacoustic tomography (OAT), motion contrast optoacoustic imaging (MC-OA), directional motion contrast optoacoustic imaging (DMC-OA), localization optoacoustic tomography (LOT), and velocity mapping were conducted in mice to evaluate cerebral, testicular, and tumor vasculature. A raster scanning approach enabled large-scale brain imaging with 9-position coverage. <b>Results:</b> MCs displayed strong optoacoustic contrast, low cytotoxicity, and long circulation times (>45 min). <i>In vivo</i> LOT imaging revealed super-resolved microvascular networks in brain, testis, and tumor, with up to 2.5-fold enhancement in vessel visualization parameters. Velocity maps enabled quantification of cerebral blood flow, and oxygenation maps were further rendered by integrating LOT with spectral unmixing. Extended imaging was enabled by persistent MC signal, facilitating full-cortex vascular imaging.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6412-6427"},"PeriodicalIF":12.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302883","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":"Regulation of heart regeneration by LSD1 through suppressing CEND1.","authors":"Huahua Liu, Jinling Dong, Shuang Liu, Yuru Luo, Yuan Fang, Hongyu Su, Weihao Xue, Rui Zhou, Wenjun Huang, Baochang Lai, Ying Xiong, Shuangshuang Wang, Lingli Liang, Zhen Wang, Donghong Zhang, Lianpin Wu, Yanmin Zhang, Bin Zhou, John Y-J Shyy, Zuyi Yuan, Yidong Wang","doi":"10.7150/thno.110297","DOIUrl":"10.7150/thno.110297","url":null,"abstract":"<p><p><b>Rationale:</b> Improving heart regeneration through reactivating cardiomyocyte proliferation holds a great potential for repairing diseased hearts. We recently reported that LSD1-dependent epigenetic repression of Cend1 transcription is prerequisite for cardiomyocyte proliferation and mouse heart development. This study interrogates the potential role of this LSD1-CEND1 axis in heart regeneration and repair. <b>Methods:</b> The cardiomyocyte-specific Lsd1 knockout or overexpression mice, Cend1 null mice and cardiomyocyte-specific Cend1 overexpression mice were used to determine the role of LSD1-CEND1 axis in heart regeneration after experimental injuries. Neonatal and adult mice were subjected to apical resection or left anterior descending coronary artery ligation, respectively, to establish cardiac injury models. Echocardiography and Masson staining were employed to assess cardiac function and histopathology, respectively. The molecular changes were determined using RNA sequencing, quantitative RT-PCR, Western blotting and immunostaining. <b>Results:</b> Cardiomyocyte-specific deletion impeded neonatal heart regeneration, while overexpression of Lsd1 had the opposite effect. RNA sequencing revealed that Cend1, a crucial suppressor of cardiomyocyte cycling, was the most significantly elevated gene induced by Lsd1 loss during heart regeneration. Cardiomyocyte-specific Cend1 overexpression hindered neonatal heart regeneration, while Cend1 loss in nullizygous mice had the opposite effect. Cend1 deletion resulted in gene expression alterations associated with enhanced cardiomyocyte proliferation, neovascularization, and macrophage activation. Furthermore, the cardiac regeneration defect caused by Lsd1 loss was not observed when experiments were performed with mice that were nullizyogus for Cend1. Moreover, we found that either Lsd1 overexpression or Cend1 deletion could promote heart regeneration and repair, and improve cardiac function following experimental myocardial infraction in adult mice. <b>Conclusion:</b> Our results demonstrate that LSD1-dependent suppression of CEND1 is crucial for heart regeneration in neonatal and adult mice after experimental injury. These findings suggest LSD1 activation and CEND1 inhibition as promising therapeutic strategies to enhance endogenous cardiac repair in humans.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6313-6328"},"PeriodicalIF":12.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302821","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":"Extrachromosomal circular DNA drives dynamic genome plasticity: emerging roles in disease progression and clinical potential.","authors":"Bin Shi, Ping Yang, Huaijin Qiao, Daojiang Yu, Shuyu Zhang","doi":"10.7150/thno.111765","DOIUrl":"10.7150/thno.111765","url":null,"abstract":"<p><p>Extrachromosomal circular DNA (eccDNA) has emerged as a dynamic and versatile genomic element with key roles in physiological regulation and disease pathology. This review synthesizes current knowledge on eccDNA, covering its classification, biogenesis, detection methods, biological functions, and clinical implications. Once considered rare anomalies, eccDNAs are now recognized as major drivers of oncogene amplification, genomic plasticity, and therapeutic resistance, particularly in cancer. EccDNA subtypes such as microDNA, double minutes, and ecDNA are defined by their structural, genomic, and pathological features. EccDNAs originate through diverse mechanisms including DNA repair, chromothripsis, breakage fusion bridge cycles, and apoptosis, occurring in both normal and stressed cells. Advances in long-read and single-cell sequencing, CRISPR-based synthesis, and computational tools have improved detection and functional analysis. Functionally, eccDNAs contribute to transcriptional amplification, activate immune responses through cGAS-STING signaling, and facilitate intercellular communication. They are found across a range of tissues and disease states-including cancer, cardiovascular, neurological, autoimmune, and metabolic disorders-and serve as both biomarkers and regulatory elements. We introduce the concept of the stress selection theory, which proposes eccDNA as an adaptive reservoir that enhances cellular fitness in response to environmental and therapeutic pressures. Despite growing insights, challenges remain in understanding tissue-specific roles, achieving clinical translation, and standardizing methodologies. Emerging tools in multi-omics, spatial biology, and artificial intelligence are expected to drive future breakthroughs in precision medicine.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6387-6411"},"PeriodicalIF":12.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302872","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":"Boosting mRNA cancer vaccine efficacy via targeting <i>Irg1</i> on macrophages in lymph nodes.","authors":"Wenwen Wei, Xiao Yang, Yeshan Chen, Mengjie Che, Ying Ye, Yue Deng, Mengyao Su, Yajie Sun, Jingshu Meng, Yan Hu, Jiacheng Wang, Yijun Wang, Zishan Feng, Zhiyuan Zhou, Yan Li, Qian Li, Zhanjie Zhang, Bian Wu, Haibo Zhang, You Qin, Lu Wen, Chao Wan, Kunyu Yang","doi":"10.7150/thno.110305","DOIUrl":"10.7150/thno.110305","url":null,"abstract":"<p><p><b>Rationale:</b> mRNA cancer vaccines show great promise for tumor therapy, but the therapeutic efficacy is limited. Metabolites play critical roles in immunomodulation. However, their role in mRNA cancer vaccines remains poorly understood. <b>Methods:</b> Metabolome analysis and single-cell RNA sequence were performed to explore the most important metabolite and its source cell. B16-F10-OVA-bearing wide-type and <i>Irg1</i>-depleted C57BL/6 mice were treated with OVA-LNP, OVA&si-Irg1-LNP, or anti-PD-1 antibody to evaluate therapeutic efficacy. Flow cytometry analysis was used to examine the immune cells within the lymph nodes, spleens, and the tumor immune environment. <b>Results:</b> We found that macrophage-derived itaconate was increased markedly in activated ipsilateral lymph nodes after ovalbumin-encoding mRNA-lipid nanoparticle (OVA-LNP) injection, compared to homeostatic contralateral lymph nodes. Depleting the immune-responsive gene 1(<i>Irg1</i>), which encodes the itaconate-production enzyme aconitate decarboxylase (ACOD1), in macrophages improved dendritic cell antigen presentation and enhances T cell function. Combining <i>Irg1</i> knockdown via small interfering RNA (siRNA) with OVA mRNA in LNPs augmented the therapeutic efficacy of mRNA cancer vaccines, both as monotherapy and in combination with an anti-programmed cell death-1 antibody. <b>Conclusions:</b> Our findings reveal a link between itaconate and mRNA cancer vaccines, suggesting that targeting <i>Irg1 via</i> siRNA-LNP could be a promising strategy to improve the therapeutic efficacy of mRNA cancer vaccines.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6329-6346"},"PeriodicalIF":12.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302866","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":"Breaking the premetastatic niche barrier: the role of endothelial cells and therapeutic strategies.","authors":"Yingshuai Fang, Wenming Cui, Yabing Yang, Xinhao Zhang, Mengyao Tian, Zhiyuan Xie, Ying Guo, Weitang Yuan, Zhen Li, Shuaixi Yang","doi":"10.7150/thno.113665","DOIUrl":"10.7150/thno.113665","url":null,"abstract":"<p><p>The premetastatic niche (PMN) represents a metastasis-facilitative microenvironment established prior to tumor dissemination, initiated by vascular leakage and endothelial cell (EC) functional remodeling. ECs play pivotal roles as bridges in different stages of the metastatic cascade. As critical stromal components within the PMN, ECs not only drive angiogenesis but also actively orchestrate immune suppression, extracellular matrix (ECM) remodeling, and the inflammatory signaling characteristic of PMN formation, with multiple specific signaling pathways such as VEGF/Notch playing a crucial role. With the evolving understanding of the role of ECs in controlling tumor metastasis, therapeutic strategies targeting ECs within the PMN, such as antiangiogenic therapy (AAT), targeting of endothelial glycocalyx (GCX), inhibition of tumor-derived exosome (TDE) and angiocrine signaling, are becoming research hotspots. This review systematically delineates the cellular and molecular composition of PMNs, dynamically dissects their spatiotemporal evolution, and highlights organ-specific mechanisms of EC-driven PMN establishment. Furthermore, we summarize emerging EC-targeted therapeutic strategies, providing innovative insights for inhibiting tumor metastasis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 13","pages":"6454-6475"},"PeriodicalIF":12.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302867","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}