Theranostics最新文献

{"title":"Structure-based redesign enables clinical translation of CAIX-targeted theranostics in clear cell renal cell carcinoma.","authors":"Zexin Xu, Hui Zhou, Ye Dong, Dan Feng, Baocheng Chen, Hongxin Li, Ruitao Yang, Ningjie Li, Yuting Cao, Hankuan He, Han Wu, Yuhua Zhong, Hubing Wu, Liang Zhao, Haojun Chen, Kongzhen Hu","doi":"10.7150/thno.134970","DOIUrl":"10.7150/thno.134970","url":null,"abstract":"<p><p>Carbonic anhydrase IX (CAIX) is an interesting therapeutic target in clear cell renal cell carcinoma (ccRCC), but gastrointestinal uptake impedes the clinical translation of CAIX-targeted radioligand. In this study, structure-guided optimization of a cyclic peptide scaffold was conducted to decouple tumor targeting from gastrointestinal retention.</p><p><strong>Methods: </strong>Five novel CAIX-targeting ligands were developed at the base of a cyclic peptide and evaluated in OS-RC-2 cell, small animal positron emission tomography/computed tomography (PET/CT), biodistribution, and radiotherapy experiments. The lead candidate was tested on 21 patients with cancer in comparison to ¹⁸F-FDG.</p><p><strong>Results: </strong>In preclinical experiments, ⁶⁸Ga/¹⁷⁷Lu-ZH2 exhibited sub-nanomolar CAIX affinity and a favorable pharmacokinetics, with preserved tumor uptake and markedly reduced gastrointestinal retention, compared with benchmark ⁶⁸Ga/¹⁷⁷Lu-DPI-4452. In mice, ¹⁷⁷Lu-ZH2 inhibited tumor growth and prolonged survival without evident toxicity. In a first-in-human study of 21 patients with renal masses, ⁶⁸Ga-ZH2 PET/CT was deemed safe and demonstrated a superior diagnostic performance to ¹⁸F-FDG, detecting additional primary tumors and metastases with higher contrast.</p><p><strong>Conclusions: </strong>These results establish ⁶⁸Ga/¹⁷⁷Lu-ZH2 as a CAIX-targeted imaging and potential therapeutic agent with favorable preclinical and early clinical imaging characteristics, enabling the sensitive detection of ccRCC and laying the groundwork for further therapeutic investigation.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8247-8262"},"PeriodicalIF":14.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679945","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 reproducible ultrasound localization microscopy framework for the quantitative imaging of hepatocellular carcinoma on a clinical ultrasound system.","authors":"Jiajia Tang, Huazhen Liu, Baoluhe Zhang, Shunda Du, Long Zou, Jinghui Liang, Meng Yang","doi":"10.7150/thno.133561","DOIUrl":"10.7150/thno.133561","url":null,"abstract":"<p><strong>Rationale: </strong>Poor differentiation and microvascular invasion (MVI) are crucial prognostic indicators for hepatocellular carcinoma (HCC), but evaluating them before surgery is still difficult. Our goal was to develop a reproducible framework for ultrasound localization microscopy (ULM) using a clinical ultrasound system and assess its effectiveness in predicting tumor differentiation and MVI.</p><p><strong>Methods: </strong>Participants were prospectively enrolled and underwent contrast-enhanced ultrasound and ULM imaging. We first compared frame selection strategies by calculating coefficients of variation (COVs) of ULM parameters derived from motion-variance curve (MVC) alone versus MVC combined with time-intensity curve (TIC). ULM resolution and parameter stability were then assessed across low (0-399), medium (400-699), and high (700-1000) frame counts. Regions of interest (ROIs) were manually drawn on grayscale ultrasound and mapped to ULM images. Inter-operator agreement was evaluated using intraclass correlation coefficients (ICCs). Participants were grouped by pathological differentiation and MVI status. The predictive performance of ULM parameters was assessed with multivariable logistic regression.</p><p><strong>Results: </strong>Sixty-one HCC participants were enrolled (11 poorly differentiated, 50 well differentiated; 30 MVI-positive, 31 MVI-negative). The MVC+TIC strategy yielded significantly lower COVs, indicating higher repeatability of ULM parameters. Medium frame counts (400-699) provided high resolution (minimum vessel diameter 91.3 ± 22.7 μm) and stable parameters (COV < 20%), and were therefore selected for ULM reconstruction. All ULM parameters showed high inter-operator agreement (ICC 0.876-0.988). Based on the established ULM framework, higher intratumoral mean curvature was independently associated with poor differentiation [area under the curve (AUC) 0.91], and higher peritumoral mean curvature independently predicted MVI status (AUC 0.78).</p><p><strong>Conclusion: </strong>The reproducible ULM framework enables stable, high-resolution microvascular imaging of HCC. ULM-derived parameters hold potential as novel biomarkers for predicting differentiation grade and MVI status of HCC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8230-8246"},"PeriodicalIF":14.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680057","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":"Surface-cleaned black phosphorus nanosheets chelate iron and rebalance the ferroptosis-immune axis in acute kidney injury.","authors":"Wan-Lin Tan, Jin-Ming Zhu, Xiao-Xiao Xu, Jing Jia, Rong-Yu Chen, Xiong Yu, Lu-Qun Liang, Yuan-Yuan Ruan, Fang-Fang Wang, Yu-Ting Chen, Yu-Lin Peng, Jin Peng, Dan Wang, Ling-Ling Liu, Yao Ran, Bing Guo, Jian Feng, Yuan-Yuan Wang","doi":"10.7150/thno.129807","DOIUrl":"10.7150/thno.129807","url":null,"abstract":"<p><strong>Rationale: </strong>Nanomaterials have been explored for acute kidney injury (AKI) therapy because of their ability to scavenge reactive oxygen species (ROS) and reduce oxidative stress. Black phosphorus nanosheets (BPNSs) show renoprotective potential, but spontaneous surface oxidation may weaken their redox activity and therapeutic efficacy. It remains unclear whether surface engineering can improve the biological activity of BPNSs and modulate ferroptosis and immune activation during AKI.</p><p><strong>Methods: </strong>Surface-cleaned BPNSs (sc-BPNSs) were prepared by hydrogen reduction and characterized. Fluorescence-labeled sc-BPNSs were used to examine biodistribution, and therapeutic efficacy was evaluated in mice with AKI. <i>In vitro</i>, mouse renal tubular epithelial cells (mRTECs) were subjected to hypoxia/reoxygenation (H/R). Ferroptosis and iron homeostasis were assessed using biochemical, histological, and imaging assays. RNA sequencing was performed in mRTECs and macrophages to identify pathways affected by sc-BPNSs. A tubular epithelial cell-macrophage co-culture model was used to examine intercellular crosstalk after injury.</p><p><strong>Results: </strong>Hydrogen reduction produced sc-BPNSs with reduced surface oxidation, stronger antioxidant activity, and improved renal accumulation. After intravenous administration, sc-BPNSs preferentially accumulated in injured kidneys, reduced ROS accumulation and lipid peroxidation, alleviated tubular injury, and improved renal function. Transcriptomic analysis showed that sc-BPNSs affected pathways related to oxidative stress, iron metabolism, and immune regulation. Mechanistically, sc-BPNSs restored iron homeostasis by sequestering labile iron and regulating transferrin receptor 1/2 (TFR1/TFR2) and ferroportin (FPN1), thereby suppressing ferroptosis <i>in vitro</i> and <i>in vivo</i>. sc-BPNSs also inhibited Ras-MAPK signaling, reduced M1 macrophage activation, and increased M2-associated marker expression. In the co-culture model, sc-BPNSs attenuated the ferroptotic and inflammatory crosstalk between injured tubular epithelial cells and macrophages.</p><p><strong>Conclusions: </strong>sc-BPNSs protect against AKI by reducing oxidative stress, restoring iron homeostasis, suppressing ferroptosis, and modulating macrophage activation. These findings suggest that surface-cleaned BPNSs may provide a therapeutic approach for AKI by targeting both tubular ferroptosis and inflammatory amplification.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8151-8179"},"PeriodicalIF":14.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679937","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":"Programmable transcriptional condensates for enhanced CRISPR-based gene regulation.","authors":"Aolin Li, Congcong Cao, Chunyan Yang, Yuchen Liu","doi":"10.7150/thno.139164","DOIUrl":"10.7150/thno.139164","url":null,"abstract":"<p><strong>Rationale: </strong>Efficient gene activation or repression through programmable CRISPR-Cas9 has revolutionized molecular biology and drug development. Nonetheless, the currently available CRISPRa/i approaches are modestly potent and require multi-component delivery, which hampers the wide use of the technology in both research and therapy.</p><p><strong>Methods: </strong>We developed a modular CRISPR-condensate platform by appending a multivalent RNA nanostar to the 3' end of a single-guide RNA, producing a sgRNA-nanostar chimera that mediates phase separation at Cas9-bound genomic loci. The nanostar scaffold also contains MS2 stem-loops, which recruit MCP-tagged transcriptional effectors (VP64 for activation, KRAB for repression) to the condensate microenvironment at high local concentration. We examined condensate formation, genome targeting, and transcriptional output by using live-cell imaging, RT-qPCR, ChIP-seq, RNA-seq and CUT&Tag in HEK293T, HeLa, U-2 OS, MDA-MB-231, as well as human iPSC cell lines.</p><p><strong>Results: </strong>The CRISPR-condensate design resulted in up to 50-100-fold target-gene activation, compared with 5-10-fold activation by direct VP64 fusion, and 20-30-fold transcriptional repression, compared with 3-5-fold repression by direct KRAB fusion, with high target specificity (12 versus 28 non-target differentially expressed genes assessed by RNA-seq). Orthogonal kissing-loop (KL) pairings enabled independent condensate systems for simultaneous activation and repression of multiplexed targets. Janus condensates containing both activating and repressive domains enabled bidirectional regulation at a single locus. The system requires delivery of only three independently expressible components-dCas9-NLS, an sgRNA-nanostar chimera bearing MS2 stem-loops (MS2SLs), and an MCP-fused effector (VP64-MCP for activation or KRAB-MCP for repression)-and showed minimal innate immune response and high cell viability.</p><p><strong>Conclusions: </strong>The CRISPR-condensate system merges the dramatically enhanced transcriptional efficacy with the reduced complexity of components, providing a modular system for fine-tuned gene expression regulation. This strategy makes biomolecular condensation a general principle for enhancing CRISPR gene regulation, opening up possibilities for functional genomics, cell engineering, and therapy development.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8215-8229"},"PeriodicalIF":14.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679901","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":"Emerging trends in bone marrow organoid research: From hematopoietic microenvironment reconstruction to translational and regenerative theranostic applications.","authors":"Heebin Park, Jaemin Jeong","doi":"10.7150/thno.137874","DOIUrl":"10.7150/thno.137874","url":null,"abstract":"<p><p>Bone marrow organ is characterized as a dynamic tissue with a complex microenvironment wherein hematopoietic stem cell (HSC) homeostasis is maintained, and the generation of various hematopoietic cell subsets is regulated. Organoids technology has been applied as an alternative tool for modeling complex tissue microenvironments in a laboratory setting through the self-organization of cells. Recent studies have established a platform capable of studying complex cellular interactions by generating bone marrow organoids (BMOs) from iPSCs. Moreover, BMOs can emulate the architecture observed of the bone marrow, including the various cell types, containing vascular-like networks, HSCs, mesenchymal stromal cells (MSCs), and mature hematopoietic cells. This review aimed to summarize how BMOs can provide foundational data essential for understanding similarities in the microenvironment and the pathological mechanisms underlying bone marrow diseases, as well as for developing new treatments. Furthermore, BMO systems represent a cutting-edge platform for studying hematopoiesis, disease mechanisms, and therapeutic screening, highlighting the recent trend toward physiologically relevant organoid-based models in regenerative and hematopoietic research.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8036-8054"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680058","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":"Trop2-targeted PET/CT imaging with ⁶⁸Ga-MY6349 improves diagnostic accuracy and influences clinical management in breast cancer.","authors":"Lingyu Yu, Liang Zhao, Ru Zeng, Yonghui Su, Zhenyu Wu, Shan Yu, Yin Li, Hao Fu, Wei Guo, Yining Sun, Hannan Gao, Long Sun, Hua Wu, Feng Ye, Fan Wang, Haojun Chen","doi":"10.7150/thno.136704","DOIUrl":"10.7150/thno.136704","url":null,"abstract":"<p><p><b><i>Rationale:</i></b> Trophoblast cell-surface antigen 2 (Trop2) is an essential therapeutic target in breast cancer, yet non-invasive methods for assessing its expression and predicting response to Trop2-directed antibody-drug conjugates (ADCs) remain limited. We aimed to evaluate the diagnostic accuracy of ⁶⁸Ga-MY6349 positron emission tomography/computed tomography (PET/CT) in patients with breast cancer and assess its impact on clinical decision-making. <b><i>Methods:</i></b> We prospectively enrolled 73 patients with suspected or confirmed breast cancer who underwent both ⁶⁸Ga-MY6349 and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT from December 2024 to April 2025. Lesion-based diagnostic performance was compared using histopathology and follow-up imaging as reference standards. Treatment decisions were recorded before and after ⁶⁸Ga-MY6349 PET/CT. Serial ⁶⁸Ga-MY6349 PET/CT was performed to assess the early metabolic response in three patients with triple-negative breast cancer receiving sacituzumab tirumotecan. <b><i>Results:</i></b> ⁶⁸Ga-MY6349 PET/CT identified more malignant lesions (564 vs. 436) and fewer false positives (2 vs. 40) than ¹⁸F-FDG PET/CT. In the initial-staging cohort (n = 30), ⁶⁸Ga-MY6349 PET/CT led to TNM stage upgrades in 6/30 patients (20%) and treatment modifications in 4/30. In the restaging cohort (n = 43), clinical management was altered in 5/43 patients (12%) owing to the identification of additional metastatic lesions or rectification of false-positive findings via ⁶⁸Ga-MY6349 PET/CT. ⁶⁸Ga-MY6349 PET/CT yielded higher overall tumor uptake (median maximum standardized uptake value (SUV_max), 5.9 vs. 4.1; P < 0.001) and improved lesion conspicuity, particularly in lymph node and metastatic lesions. Exploratory analysis in three patients receiving Trop2-ADC therapy showed that early changes in ⁶⁸Ga-MY6349 uptake after two treatment cycles were concordant with the subsequent clinical response. <b><i>Conclusions:</i></b> ⁶⁸Ga-MY6349 PET/CT demonstrated superior diagnostic performance to ¹⁸F-FDG PET/CT in breast cancer staging and diagnosis, directly influencing therapeutic strategies. Preliminary findings from the triple-negative breast cancer cases suggest that early changes in SUV_max may be associated with the treatment response to Trop2-targeted ADC therapy, warranting further prospective validation in larger patient populations.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8117-8128"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679992","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":"An engineered ferritin nanocage co-delivery system for targeted hair cells protection and hearing loss attenuation.","authors":"Junying Zhang, Zhiwei Zheng, Jiaru Zhang, Xinyuan Ma, Zihao Li, Hongyan Lin, Guohui Nie, Minmin Liang, Hui Ding, Yingzi He","doi":"10.7150/thno.131600","DOIUrl":"10.7150/thno.131600","url":null,"abstract":"<p><strong>Rationale: </strong>Hearing loss is a common sensory disorder with few treatment options, mainly due to the blood-labyrinth barrier and lack of effective targeted delivery systems. Small molecules such as LLY283 and RG108 protect hair cells (HCs), but clinical use is limited by poor cellular uptake, off-target toxicity, and inefficient cochlear delivery.</p><p><strong>Methods: </strong>We developed a ferritin (Fn)-based nanocage (LR@Fn) to co-deliver RG108 and LLY283 via local injection through the round window membrane. Fn offers natural HC targeting, a hollow cavity, and good biocompatibility. Drugs were loaded using a pH-triggered strategy while maintaining structural and colloidal stability.</p><p><strong>Results: </strong>In neonatal cisplatin and adult noise-induced hearing loss models, LR@Fn reduced HCs loss, synaptic damage, and apoptosis more effectively than dexamethasone. LR@Fn treatment activated the <i>Wnt/β-catenin</i> pathway, which may contribute to the observed protective effect.</p><p><strong>Conclusions: </strong>LR@Fn is a biocompatible ferritin-based platform for targeted inner-ear therapy, showing potential for multiple forms of hearing loss.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8104-8116"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680085","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 challenges and strategies for navigating <i>in vivo</i> barriers to therapeutic bacterial delivery.","authors":"Haoda Yu, Jieyu Liu, Shuxin Zhang, Bing Wang, Kui Luo, Xian Jiang","doi":"10.7150/thno.137940","DOIUrl":"10.7150/thno.137940","url":null,"abstract":"<p><p>Bacteria have emerged as promising living therapeutics for the treatment of infections, inflammatory disorders, metabolic diseases, and neoplastic diseases. However, their clinical efficacy is often compromised by <i>in vivo</i> barriers that reduce their viability and impair their function after administration. Rational engineering can help them sustain their viability under a harsh microenvironment and enhance their targetability as well as retention, ultimately improving their functional performance <i>in vivo</i>. This review starts with a concise synopsis of current status in live bacterial therapy, with particular emphasis on the major biological barriers to their <i>in vivo</i> application. Engineering strategies for harnessing bacterial intrinsic characteristics and overcoming their specific barriers are discussed. Representative examples are then presented to illustrate how engineered live bacteria overcome these biological barriers and achieve therapeutic applications via oral, topical, intravenous, and inhalational administration. Finally, we identify the key challenges associated with translating laboratory advances into reliable and safe clinical therapeutics.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7985-8016"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680007","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":"Endothelial epigenetic senescence driven microglial activation mediates cardio-retinal neuroinflammation in heart failure.","authors":"Mengdan Wang, Shuo Zhang, Tursunjan Aziz, Shiyao Zhang, Xiao Wu, Gang Li, Yan Wang","doi":"10.7150/thno.136220","DOIUrl":"10.7150/thno.136220","url":null,"abstract":"<p><strong>Rationale: </strong>Heart failure (HF) is increasingly recognized as a systemic disorder that extends beyond the heart and affects neurovascular tissues, including the retina. However, the mechanisms by which circulating factors from HF trigger retinal neuroinflammation remain unclear.</p><p><strong>Methods: </strong>HF was induced in adult mice by transverse aortic constriction (TAC). Retinal structure and function were evaluated using optical coherence tomography (OCT) and electroretinography (ERG). Parabiosis and plasma transfer experiments were performed to assess the role of circulating factors. Endothelial senescence, microglial activation, and inflammatory signaling were analyzed using immunofluorescence, qPCR, and molecular assays. The functional relevance of TGFβ2 and microglia was tested using anti-TGFβ2 antibody administration and microglial depletion with PLX5622 treatment.</p><p><strong>Results: </strong>TAC mice exhibited pronounced retinal thinning, diminished electroretinography (ERG) amplitudes, and reduced vascular density. Exposure of healthy mice to HF plasma reproduced these abnormalities, indicating that circulating mediators drive retinal injuries. TGFβ2 levels were markedly elevated in the plasma of both patients with HF and TAC mice. Mechanistically, TGFβ2 activated the pSMAD2/EP300 pathway in retinal endothelial cells, promoting H3K9 acetylation, P21 induction, and endothelial cell senescence. Senescent endothelial cells release proinflammatory factors that activate retinal microglia, leading to hypertrophic morphology, enhanced synaptic phagocytosis, and upregulation of cytokines such as IL1β, TNFα, and IL6. Neutralization of TGFβ2 or microglial depletion markedly reduced inflammation, preserved the retinal architecture, and restored visual function.</p><p><strong>Conclusions: </strong>Elevated TGFβ2 levels in heart failure drive retinal endothelial epigenetic senescence, which secondarily activates microglia and induces neuroinflammation. Endothelial-specific disruption of TGFβ2 signaling is sufficient to protect the retina independently of primary cardiac recovery. Targeting the TGFβ2-endothelial-microglia axis may represent a promising therapeutic strategy for preventing retinal neurovascular degeneration associated with systemic cardiac disease.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8055-8076"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680020","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":"Ligand-modified multifunctional liposome-based targeted delivery platform: a multimodal cancer combination therapy strategy.","authors":"Xuehong Zhang, Yingjie Jiang, Xing Duan, Fuchun Li, Xiaozhuo Chen, Aikepaer Aikedai, Wanting Pan, Liangjie Ren, Yufei Su, Chengqi Li, Zhaoshuo Gao, Shengcai Liao, Qiang Zhang, Zhenyu Zhu, Kaipei Luo, Yingji Wang","doi":"10.7150/thno.136152","DOIUrl":"10.7150/thno.136152","url":null,"abstract":"<p><p>The combination therapies are significantly more effective than monotherapies in enhancing anticancer efficacy, reducing drug-related toxicity, and lowering the risk of drug resistance in cancer treatment. However, achieving precise delivery of the drugs to the tumor site remains a major challenge. With the deepening exploration of surface-engineered nanocarriers, ligand-modified liposomal drug delivery systems (LLDDS) are constructed by integrating the active-targeting properties of functional ligands (such as peptides, glycans, and aptamers) with the inherent advantages of liposomes. LLDDS show promise for exhibiting strong tumor-targeting capability, improving pharmacokinetics, biodistribution, and therapeutic efficacy of anticancer agents, such as chemotherapy drugs, and enabling the multifunctional integration of multiple therapeutic strategies. This review summarizes the development of liposomes and ligand-mediated surface modification strategies. More significantly, the development of multifunctional liposomes, targeted delivery, improved anticancer effectiveness, and possible anticancer mechanisms are highlighted in the discussion of LLDDS's recent advancements for integrated therapy approaches in a variety of malignancies. Lastly, the potential and difficulties of clinical translation in this ever-evolving area are examined.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7958-7984"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680029","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}