Theranostics最新文献

{"title":"Bone-Targeting Microspheres Enable Sustained Release of CD301b⁺ Macrophage-Derived Small Extracellular Vesicles to Promote Bone Repair.","authors":"Xiang Gao, Shanshan Ma, Yeying Dong, Fengkai Yang, Rui Huang, Xiudan Zheng, Zhijun Liu, Hong Zheng, Fatai Lu, Thomas Groth, Mingyan Zhao","doi":"10.7150/thno.132666","DOIUrl":"10.7150/thno.132666","url":null,"abstract":"<p><strong>Rationale: </strong>Large bone defects often exceed the body's intrinsic capacity for self-repair. Successful bone healing depends on a coordinated immune transition alongside tightly coupled angiogenesis and osteogenesis, in which macrophages play a key regulatory role. Therefore, ideal bone-regenerative materials should integrate immunomodulatory, pro-angiogenic, and osteogenic functions.</p><p><strong>Methods and results: </strong>Small extracellular vesicles (sEVs) from CD301b⁺ macrophages (CD301b⁺-sEVs) are isolated by ultracentrifugation for inclusion in a bone-targeting microsphere system fabricated by microfluidic technology through dynamic Schiff-base cross-linking of alendronate-functionalized succinylated chitosan with oxidized sodium alginate allowing pH-responsive release of CD301b⁺-sEVs. Transcriptome sequencing and comprehensive <i>in vitro</i> studies reveal that CD301b⁺-sEVs possess the ability to modulate immune homeostasis by promoting macrophage polarization toward the pro-repair M2 phenotype, upregulate angiogenic factors that can enhance vascularization as seen by HUVEC sprouting assay, and contain RNA that stimulate osteogenic differentiation of BMSCs through activation of the Akt/GSK-3β/β-catenin signaling pathway. Preclinical studies with a rat calvaria model show that microspheres loaded with CD301b⁺-sEVs significantly promote bone regeneration in comparison to microsphere controls.</p><p><strong>Conclusion: </strong>This study not only overcomes key limitations of conventional sEVs therapies such as poor retention and instability, but also provides an innovative \"targeted localization, intelligent release, and multifunctional synergy\" strategy, offering a minimally invasive and highly effective therapeutic platform for bone repair.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7514-7536"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346304","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":"Mechano-immune interactions in musculoskeletal aging: Mechanisms and translational perspectives.","authors":"Fulin Zhou, Xianglong Zhou, Jiheng Xiao, Jianhui Xiang, Yang Liu, Weicheng Chen, Hanhong Fang, Haoran Zhou, Xiao Lv, Liming Xiong","doi":"10.7150/thno.131071","DOIUrl":"10.7150/thno.131071","url":null,"abstract":"<p><p>Mechano-immunology is an interdisciplinary field that examines how mechanical forces-including endogenous tissue stresses and exogenous stimuli-modulate immune cell function in the maintenance of homeostasis and the progression of disease. As the primary load-bearing framework of the body, the musculoskeletal system depends on coordinated mechanical loading to sustain immune balance and tissue repair. With aging, reduced physical activity, progressive matrix stiffening, and impaired mechanosensing in immune-cells converge to disrupt this mechano-immune axis, undermining immune clearance, inflammatory regulation, and regenerative capacity within musculoskeletal tissues. These alterations collectively contribute to the onset and progression of osteoarthritis, osteoporosis, and other degenerative musculoskeletal disorders. This review summarizes current advances in understanding the mechanisms of mechano-immunology within the musculoskeletal system under physiological conditions and delineates its involvement in the initiation and progression of degenerative diseases. Emerging strategies, including exercise-based interventions, controlled mechanical stimulation, and biomaterial engineering approaches targeting mechano-immune pathways, are also discussed as potential means to restore musculoskeletal homeostasis during aging.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7735-7764"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346404","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":"Cardiomyocyte-derived USP20 mitigates myocardial ischemia/reperfusion injury through deubiquitinating GRP78.","authors":"Zhenfeng Cheng, Lingfeng Zhong, Miaomiao Ying, Ziyi Huang, Zexin Yang, Wenli Zhang, Zhouqing Huang, Naijin Zhang, Xudong Chen, Xiaoxi Fan, Yucong Zhang, Ruihan Zheng, Keke Ye, Shuang Lin, Weijian Huang, Guangju Zhao, Shanshan Dai","doi":"10.7150/thno.132067","DOIUrl":"10.7150/thno.132067","url":null,"abstract":"<p><p>Myocardial ischemia/reperfusion (I/R) injury remains a major clinical challenge characterized by cardiomyocyte loss and adverse remodeling after reperfusion. Ubiquitin-Specific Peptidase 20 (USP20), a deubiquitinase involved in cellular stress responses, has not been fully characterized in the ischemic heart. This study aimed to investigate the function and mechanism of cardiomyocyte-derived USP20 in myocardial I/R injury.</p><p><strong>Methods: </strong>Myocardial I/R models and hypoxia/reoxygenation (H/R)-treated cardiomyocytes were used to evaluate USP20 expression and function. Single-cell transcriptomic analysis, cardiomyocyte-specific USP20 knockout, and USP20 overexpression models were applied. Co-immunoprecipitation, LC-MS/MS, ubiquitination assays, site-directed mutagenesis, and rescue experiments were performed to define the underlying mechanism.</p><p><strong>Results: </strong>USP20 expression was markedly decreased in I/R-injured mouse hearts and H/R-treated cardiomyocytes, and USP20 was predominantly localized in cardiomyocytes. Cardiomyocyte-specific USP20 deletion aggravated myocardial injury, adverse cardiac remodeling, and cardiac dysfunction after I/R, whereas USP20 overexpression conferred significant cardioprotection. Mechanistically, USP20 directly interacted with glucose-regulated protein 78 (GRP78) and removed K63-linked polyubiquitin chains from GRP78 at K602 through its C154 active site. This deubiquitination activated GRP78, promoted adaptive endoplasmic reticulum stress responses, and reduced myocardial injury.</p><p><strong>Conclusions: </strong>These findings identify a previously unrecognized USP20-GRP78 regulatory axis that regulates endoplasmic reticulum stress responses and limits myocardial damage during I/R. USP20 may represent a potential therapeutic target for myocardial I/R injury.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7594-7612"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346250","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":"A robust asymmetric bioadhesive patch for sutureless intestinal repair to prevent anastomotic leakage and postoperative adhesion.","authors":"Ruiqi Gao, Fangfang Su, Xiaohua Li, Zhongjie He, Yanglin Pan, Yaping Zheng, Mingzhong Wang, Lijun Yuan, Jiahe Liang, Xiaoqian Li","doi":"10.7150/thno.135611","DOIUrl":"10.7150/thno.135611","url":null,"abstract":"<p><strong>Rationale: </strong>Anastomotic leakage (AL) remains a major surgical challenge that is difficult to address using hand-sewn closure alone. Robust, rapidly acting bioadhesive patches offer a promising alternative to conventional sutures and staples. However, the development of bioadhesive patches that achieve instantaneous wet-tissue adhesion while minimizing postoperative adhesion remains challenging. Innovative material designs and interdisciplinary translational strategies are therefore needed to advance bioadhesion technologies toward clinical application.</p><p><strong>Methods: </strong>Herein, we developed a translational asymmetric bioadhesive patch (ABP) that integrates a blood-repelling, hydrophobic, HBP oil-infused anti-adhesive top surface with a bioadhesive bottom surface capable of absorbing interfacial water. The physicochemical properties, mechanical performance, wet-tissue adhesion, and hemostatic capacity of the ABP were systematically evaluated through <i>in vitro</i> and <i>in vivo</i> assays. Its therapeutic efficacy for sutureless intestinal repair was further assessed in a rat colon defect model.</p><p><strong>Results: </strong>The ABP exhibited instantaneous and robust adhesion to various biological wet tissues (~10 times stronger than FDA-approved sealant Tisseel). The patch also showed excellent stretchability, sustaining more than 1000% strain without loss of elasticity. Moreover, ABP enables rapid hemostasis in injured tissues and achieved sutureless sealing and repair of intestinal defects in a rat colon injury model. Importantly, the asymmetric design reduced postoperative adhesions and attenuated foreign body reactions.</p><p><strong>Conclusions: </strong>The proposed ABP patch provides an effective solution for intestinal defects repair by enabling immediate wet-tissue attachment, non-invasive defect closure, and durable tissue sealing without the need for device removal. By combining strong bioadhesion with an anti-adhesive outer surface, this patch offers a promising translational platform for preventing anastomotic leakage while reducing postoperative adhesions and foreign body responses.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7641-7659"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346173","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":"Ultra-high-field magnetic resonance imaging reveals sex-specific recovery after ischemic stroke following treatment with three-dimensional human mesenchymal stem cell-derived extracellular vesicles.","authors":"Jamini Bhagu, Arshia Arbabian, Thurston Da Vitoria Lobo, Katherine Martinez, Dayna L Richter, Hannah Bryant, Malathy Elumalai, Yan Li, Samuel C Grant","doi":"10.7150/thno.129188","DOIUrl":"10.7150/thno.129188","url":null,"abstract":"<p><strong>Rationale: </strong>Ischemic stroke is sexually dimorphic. Biological sex can influence injury progression and response to treatment. Extracellular vesicles (EV) derived from three-dimensional (3D) human mesenchymal stem cell aggregates (3D-EV) are a promising candidate as a treatment, but their efficacy across these biological variables and <i>in vivo</i> behavior needs to be characterized. This study evaluated whether 3D-EV therapy enhances recovery following ischemic stroke in female and male models using ultra-high-field MRI and their influence on structural, ionic, and metabolic recovery.</p><p><strong>Methods: </strong>A preclinical model of transient middle cerebral artery occlusion was used to longitudinally evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO)-labeled 3D-EV or saline at reperfusion through intra-arterial injection. MRI was performed at 21.1 T, which included T₂-weighted, diffusion-weighted imaging, gradient-recalled echo imaging, and ²³Na chemical shift imaging. Proton magnetic resonance spectroscopy (¹H-MRS) was used to quantify changes in lactate, N-acetylaspartate, creatine, and choline within peri-infarct tissue. Imaging and behavioral outcomes were assessed over 21 days.</p><p><strong>Results: </strong>USPIO-labeled 3D-EV resulted in localized hypointense contrast in the ischemic striatum, indicating delivery of treatment. T₂-weighted MRI showed progressive lesion reduction, with a trend toward better recovery in females. ²³Na MRI revealed reduced sodium accumulation, with earlier ionic normalization in 3D-EV-treated animals. Diffusion recovery was observed with sex-dependent trajectories. ¹H-MRS showed lower lactate concentrations and preservation of other metabolites in EV-treated females. Behavioral differences were not significant.</p><p><strong>Conclusions: </strong>3D-EV therapy showed trends toward structural, ionic, and metabolic recovery following an ischemic insult. Ultra-high-field MRI and MRS can provide sensitive biomarkers to resolve these differences and support 3D-EV as a potential cell-free therapeutic candidate for ischemic stroke.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7698-7714"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345708","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":"CDK9 degrader induces BRCAness and sensitizes castration-resistant prostate cancer to PARP inhibitor.","authors":"Jiaxuan Li, Jingya Sun, Weisong Tan, Guoqi Li, Wenjie Xiao, Jiajun Wu, Wei Yang, Changqing Chen, Yang Li, Jiakuan Liu, Yuanyu Liu, Dong Liu, Xiao-Hua Chen, Rujian Zhu, Ruimin Huang, Jun Yan","doi":"10.7150/thno.131907","DOIUrl":"10.7150/thno.131907","url":null,"abstract":"<p><strong>Rationale: </strong>Castration-resistant prostate cancer (CRPC) poses significant therapeutic challenges due to its aggressive nature and limited effective treatments. Although PARP inhibitor olaparib has been approved for metastatic CRPC patients bearing BRCA1/2 mutations, its application is confined to this specific patient subpopulation. The induction of \"BRCAness\" feature in CRPC patients without BRCA1/2 mutations becomes a significant challenge.</p><p><strong>Methods: </strong>A transcriptomic analysis to identify potential \"BRCAness\" regulator was performed on 921 prostate cancer (PCa) patients from 6 public datasets and validated in our own cohort. D45, a selective small-molecule protein degrader for cyclin-dependent kinase 9 (CDK9), alone or combined with olaparib, was applied in CRPC cell lines (C4-2 and 22Rv1) lacking BRCA1/2 mutations for cell viability, colony formation and apoptosis-related assays. \"BRCAness\" phenotype was characterized by Western blotting and γH2AX foci accumulation assays. RNA-seq and CUT&Tag assays were used to reveal how D45 regulated homologous recombination repair (HRR)-related genes.</p><p><strong>Results: </strong>We found the transcriptional regulator CDK9 was overexpressed in CRPC and correlated with advanced Gleason scores, metastasis, and poor prognosis. D45 treatment decreased cell survival, and led to downregulation of HRR-related genes (BRCA1/2 and RAD51) with the reduced recruitment of phosphorylated-RNA polymerase II (pSer2) to the ends of these genes with increased DNA damage, indicating a \"BRCAness\" phenotype induction. The synthetic vulnerability synergized with D45 plus olaparib was thus tested <i>in vitro</i>, showing the enhanced apoptosis in CRPC cells. Moreover, sequential D45 and olaparib administration significantly suppressed 22Rv1 xenograft growth <i>in vivo</i> (<i>P</i> < 0.001), reduced RAD51 expression and increased DNA damage. Toxicity was tolerable and consistent with prior reports. Their synergistic effect was confirmed in <i>ex vivo</i> explants from human PCa specimens.</p><p><strong>Conclusions: </strong>Our findings demonstrated CDK9 as a master regulator of BRCAness and proposed targeting CDK9 as a potential strategy to sensitize CRPC patients without BRCA1/2 mutations to PARP inhibition.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7495-7513"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346236","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":"Understanding immune checkpoint inhibitors-related myocarditis: Mechanisms and targeted therapeutic pathways.","authors":"Wenxiao Xia, Huan Zhang, Libo Liu, Chenchen Tu, Xiantao Song","doi":"10.7150/thno.127500","DOIUrl":"10.7150/thno.127500","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI)-related myocarditis is a rare but often fatal adverse event that has gained increasing attention due to the widespread clinical use of ICIs. This review explores the development of immune cells and their critical roles in cardiac autoimmunity, with particular focus on defects in central tolerance, the role of immune checkpoints, T cell trafficking to the heart, and the involvement of resident cardiac macrophages. It also introduces the key pathogenic mechanisms of ICI-related myocarditis, including the activation of autoreactive T cells that recognize self or shared antigens, the crosstalk between T cells and macrophages, and macrophage polarization. In addition, we also discuss current and emerging targetable therapeutic pathways, including cytokine modulation, the JAK/STAT pathway, and the use of CTLA-4 immunoglobulin. We further summarize practical diagnostic and prognostic approaches, including the role and limitations of troponin-based monitoring, echocardiography, magnetic resonance imaging, PET-CT applications, and endomyocardial biopsy. This review aims to establish a mechanistic framework that integrates pathogenic mechanisms, diagnostic and prognostic approaches, and therapeutically targetable pathways in ICI-related myocarditis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7715-7734"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346069","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":"Cellular senescence in musculoskeletal diseases: biological mechanisms and clinical implications.","authors":"Bingfei Li, Wanwan Qi, Bin Zhang, Shuo Ma, Wei Zhang, Caihua Zhang, Wei Xiang, Ran Chen, Chuanqing Bai, Jun Fei, Changyue Gao, Zhenhong Ni, Siru Zhou","doi":"10.7150/thno.130018","DOIUrl":"10.7150/thno.130018","url":null,"abstract":"<p><p>Cellular senescence is a persistent state of irreversible growth arrest that occurs when cells encounter various stress signals. It is marked by elevated expression of cell cycle inhibitors, dysregulated gene transcription, and secretion of the senescence-associated secretory phenotype (SASP). These senescent features may exert both detrimental and beneficial effects on tissue homeostasis and systemic physiological integrity. In this review, the relevant pathological processes are categorized into three tissue types: skeletal muscle, bone, and cartilaginous tissue. We systematically delineate the mechanisms of cellular senescence underlying seven musculoskeletal diseases, including skeletal muscle injury and regeneration, sarcopenia, osteoporosis, fracture, osteonecrosis of the femoral head (ONFH), osteoarthritis (OA), and intervertebral disc degeneration (IDD), with a particular focus on the heterogeneity of senescent cells across distinct musculoskeletal diseases. On this basis, we further elaborated on relevant mechanisms and senescence-related targets, and analyzed senescence heterogeneity in diverse musculoskeletal tissues, senescence identification and integrated diagnostic approaches. Moreover, we discussed convergent pathways, the dual roles of senescent cells, and the critical evaluation of disease-specific versus common therapeutic vulnerabilities.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7660-7697"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346268","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":"TAM-targeted nanomedicine in cancer: biological basis, therapeutic strategies, and translational perspectives.","authors":"Lili Zhou, Fang Yuan, Yangyang Wu, Xin Li, Debiao Xiang","doi":"10.7150/thno.132714","DOIUrl":"10.7150/thno.132714","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) are the most common immune cell type found in the tumor microenvironment. They are also key participants in the regulation of angiogenesis, metastasis, immune evasion, and therapeutic resistance. Recent single-cell transcriptomics and spatial profiling have shown that TAMs are extremely heterogeneous and functionally plastic beyond the traditional M1/M2 paradigm, and that more refined therapeutic strategies are required. Nanomedicine can integrate macrophage biology, the tumor microenvironment, and the engineering of the delivery system to design TAM-oriented interventions. With optimization of delivery systems (e.g. particle size, surface chemistry, ligands, therapeutic payloads, and the type of stimuli), multiple functionalities can be engineered to improve macrophage (in the tumor microenvironment) recruitment, depletion, reprogramming, and enhancement of TAM phagocytosis, antigen presentation, and immune regulation. Nanoparticles with biomimetic systems, macrophage membrane coating, as well as macrophage-derived extracellular vesicles and engineered exosome platforms, can also provide a wide array of options for TAM-oriented therapy. In this review, we provide an overview of the origin, heterogeneity, and functions of TAMs in cancer, and categorize TAM-targeted nanotherapeutics based on the principal approaches of recruitment blockade, tumor-promoting macrophage depletion, reprogramming, functional enhancement of phagocytosis and immune activation, and biomimetic drug delivery. We also present a comparison of representative nanoplatforms, highlight the latest clinical developments, and investigate key barriers to moving research from the lab to the clinic using nanomedicine, including delivery system design focused on targeting TAMs, safe and effective delivery to tumors, off-target effects on macrophages, ease of manufacture, and control of product quality. By combining TAM biology with the design of specialized nanocarriers and clinical research, this review outlines the main directions of research and provides a practical approach to the development of specialized TAM-targeted cancer nanomedicines.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7537-7570"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345688","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":"Peripheral blood immune profiling reveals key signatures in newly diagnosed NK/T cell lymphoma patients.","authors":"Dahui Li, Hongyuan Zou, Mingyu Wang, Na Tian, Chuanxu Liu, Wenhao Zhang, Shiyu Jiang, Ruiliang Zhu, Xiangyu Yang, Fangxia Li, Ying Gao, Wendi Wei, Ran Jia, Zihan Jiang, Yuanhua Liu, Rong Tao, Xiaozhen Liang","doi":"10.7150/thno.132582","DOIUrl":"10.7150/thno.132582","url":null,"abstract":"<p><strong>Rationale: </strong>Natural killer/T-cell lymphoma (NKTCL) is an aggressive Epstein-Barr virus (EBV)-associated non-Hodgkin lymphoma with a poor prognosis. Recent genomic and transcriptomic studies of tumor tissues have advanced our understanding of NKTCL pathogenesis, but the systemic immune profile at initial diagnosis remains incompletely elucidated.</p><p><strong>Methods: </strong>In this study, we characterized the immune landscape of peripheral blood mononuclear cells (PBMCs) from 20 newly diagnosed NKTCL patients and 12 healthy donors using single-cell RNA sequencing and confirmed our results through flow cytometry and PrimeFlow.</p><p><strong>Results: </strong>We identified a distinct proliferative-NK/T (Proli-NK/T) cell subset in NKTCL, characterized by high expression of cell cycle-related genes but lacking a malignant phenotype. Additionally, we observed a reduction in total and classical memory B cells, accompanied by enrichment of apoptosis and cell differentiation signatures. NK cells showed increased expression of HLA class II and activation markers, along with enhanced predicted interactions with CD4⁺ T cells. The decrease of naive CD4⁺ T cells might imply their skewed differentiation into Th1 and Th17 cells, while expansion of granzyme K (GZMK⁺)-expressing CD8⁺ central memory T cells was associated with interferon-γ-driven responses. Patients with a high intracellular EBV load exhibited accumulation of highly cytotoxic CD56^dim <i>_PTPRCAP</i> NK cells and GZMK⁺ GZMB⁺ CD8⁺ effector memory T cells, along with a marked depletion of memory B cells. This implies a correlation between intracellular EBV burden and peripheral immune dysregulation in NKTCL.</p><p><strong>Conclusions: </strong>We have uncovered the dynamic changes in PBMCs of newly diagnosed NK/T cell lymphoma patients and identified specific characteristics in patients with high intracellular EBV levels. Our findings provide new insights into the immunopathogenesis of NKTCL, offering valuable information for immune-based stratification and the development of therapeutic strategies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7626-7640"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346369","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}