Theranostics最新文献

{"title":"CAIX-targeted α therapy directed against hypoxic tumor cells in combination with immune checkpoint inhibitors in a syngeneic mouse tumor model.","authors":"Sylvia T M Wenker, Mark W Konijnenberg, Daphne Lobeek, Giulia Tamborino, Janneke D M Molkenboer-Kuenen, Gerben M Franssen, Daan F Boreel, Simone C Kleinendorst, Hans Peters, Johan Bussink, Sanne A M van Lith, Sandra Heskamp","doi":"10.7150/thno.127288","DOIUrl":"10.7150/thno.127288","url":null,"abstract":"<p><p>Tumor hypoxia is a major factor in therapy resistance. A potential strategy to treat hypoxic tumors is targeted α therapy (TAT), since α particles can cause complex DNA damage independent of oxygen levels. Here, we investigate the potential of TAT as monotherapy and in combination with immune checkpoint inhibitors (ICI) to treat hypoxic tumors.</p><p><strong>Methods: </strong>Monoclonal anti-CAIX antibody DOTA-MSC3 was labeled with indium-111 (¹¹¹In) or actinium-225 (²²⁵Ac), and binding to CAIX-expressing hypoxic tumor cells was determined <i>in vitro</i>. Subsequently, the <i>in vivo</i> biodistribution and dosimetry of radiolabeled DOTA-MSC3 was assessed in B16F10-OVA tumor-bearing mice, and its spatial distribution in the tumor (autoradiography) was correlated to CAIX expression measured by immunofluorescence. Finally, tumor growth and survival were determined upon treatment with [²²⁵Ac]Ac-DOTA-MSC3 with and without ICI.</p><p><strong>Results: </strong>¹¹¹In- and ²²⁵Ac-labeled DOTA-MSC3 bound specifically to CAIX-expressing hypoxic tumor cells. <i>In vivo</i>, uptake of both radiopharmaceuticals in B16F10-OVA tumors was spatially correlated with CAIX-positive hypoxic tumor regions. [²²⁵Ac]Ac-DOTA-MSC3 significantly prolonged survival of mice compared with PBS control (p=0.0032). Furthermore, the combination of [²²⁵Ac]Ac-DOTA-MSC3 and ICI significantly delayed tumor growth and prolonged survival compared with PBS control (p=0.0022 and p=0.0019, respectively).</p><p><strong>Conclusion: </strong>Overall, these results demonstrate first proof-of-concept of the potential of CAIX-TAT to treat hypoxic tumors by targeting CAIX-positive hypoxic tumor regions. CAIX-TAT combined with ICI was most effective in inhibiting tumor growth and prolonging survival of tumor-bearing mice. Future studies are required to investigate the radiobiological and immunological effects of CAIX-TAT, to guide optimization of this treatment in combination with ICI.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4508-4520"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378616","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":"Connective tissue growth factor contributes to resistance to anti-angiogenic therapies in renal cancer.","authors":"Manon Teisseire, Arthur Karaulic, Julien Parola, Maëva Totobesola, Delphine Borchiellini, Tanguy Pace-Loscos, Renaud Schiappa, Emmanuel Chamorey, Jérôme Durivault, Maëva Dufies, Damien Ambrosetti, Frédéric Luciano, Juan Gao, Yihai Cao, Gilles Pagès, Sandy Giuliano","doi":"10.7150/thno.125269","DOIUrl":"10.7150/thno.125269","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is predominantly treated with anti-angiogenic therapies (AATs), such as sunitinib and axitinib. While these therapies initially improve outcomes, resistance frequently emerges, limiting long-term efficacy. Understanding the molecular mechanisms underlying AAT resistance is essential to optimize treatment strategies.</p><p><strong>Methods: </strong>To identify factors involved in AAT resistance, we performed integrated transcriptomic and proteomic analyses on ccRCC cell lines subjected to either transient AAT treatment or with established acquired resistance. Functional validation was performed using <i>in vitro</i> assays (proliferation, migration, invasion) and <i>in vivo</i> zebrafish models. Plasma levels of candidate proteins were also measured in ccRCC patients and correlated with clinical outcomes.</p><p><strong>Results: </strong>Connective Tissue Growth Factor (CTGF) was consistently upregulated following treatment and in resistant cell lines. CTGF, a secreted protein regulated by Yes-associated protein (YAP) in the Hippo pathway, is known to promote angiogenesis, fibrosis, and tumor progression. Functionally, CTGF enhanced tumor cell aggressiveness <i>in vitro</i> and <i>in vivo</i>. Patient-derived samples also exhibited elevated CTGF levels in resistant tumors. Crucially, higher plasma CTGF levels were associated with shorter progression-free survival in ccRCC patients receiving AATs.</p><p><strong>Conclusion: </strong>CTGF is a key mediator of resistance to AATs in ccRCC, by promoting tumor progression and remodeling the tumor microenvironment. CTGF may thus serve as both a predictive biomarker and a therapeutic target. These findings support further investigation of CTGF inhibition as a strategy to overcome AAT resistance and improve treatment outcomes in ccRCC patients.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4489-4507"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378630","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":"Panoramic description of ROS-based nanotechnology for osteomyelitis therapy: Challenges, opportunities, and prospects.","authors":"Wenqiao Wang, Xiaoying Kong, Jinsheng Shi, Ting Wang","doi":"10.7150/thno.124716","DOIUrl":"10.7150/thno.124716","url":null,"abstract":"<p><p>Osteomyelitis, an inflammatory disease of bone and bone marrow caused by infectious microorganisms, has long been a major clinical challenge due to the lack of consistently effective treatment strategies. Conventional therapeutic approaches, such as antibiotic therapy and surgical debridement, are frequently associated with the development of antibiotic resistance and a high risk of disease recurrence, thereby complicating long-term clinical management. In recent years, reactive oxygen species (ROS)-based nanotechnology has emerged as a promising therapeutic modality for osteomyelitis, garnering considerable attention for the potential to overcome antibiotic resistance. This review summarizes the epidemiological characteristics, current treatment approaches, and pathogenic mechanisms of osteomyelitis, and comprehensively examines advances in ROS nanotechnologies for osteomyelitis treatment. In addition, the technical advantages and limitations of major ROS-based strategies, including photodynamic therapy (PDT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), and microwave dynamic therapy (MWDT), are systematically discussed to provide guidance for further optimization of ROS-mediated strategies. Furthermore, the therapeutic potential of these strategies in antimicrobial activity, promotion of tissue repair, and immune regulation is analyzed, offering theoretical support for the integration of ROS-based strategies with existing treatment modalities for improved management of osteomyelitis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4657-4701"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378658","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":"Subtype-Specific Roles of Anterior Cingulate Cortex Neurons in Pain-Induced Social Deficits in Mice.","authors":"Xiangdong Wan, Ziqian Yan, Zhaoyichun Zhang, Xueqing Liu, Dingding Yang, Ming Zhang, Haiying Liu, Jiaqi Li, Bo Yang, Rong Zheng, Yifan Lu, Jing Huang, Fan Zhang, Guohong Cai, Shengxi Wu","doi":"10.7150/thno.129482","DOIUrl":"10.7150/thno.129482","url":null,"abstract":"<p><strong>Rationale: </strong>Pain is frequently accompanied by impairments in social behavior; however, the neural circuitry underlying pain-induced social deficits remains poorly understood. The aim of the present study was to delineate the distinct functional roles of γ-aminobutyric acid-releasing (GABAergic) neurons and calcium/calmodulin-dependent protein kinase II-positive (CaMKII⁺) neurons in the anterior cingulate cortex (ACC) in mediating pain-induced social deficits.</p><p><strong>Methods: </strong>Mouse models of inflammatory and neuropathic pain were employed. Optogenetic and chemogenetic approaches, combined with fiber photometry, were used to manipulate and monitor the activity of ACC neuronal subtypes. Social behaviors were assessed using the three-chamber social interaction test. Mechanical and thermal pain sensitivity were evaluated using von Frey filaments and the Hargreaves test, respectively.</p><p><strong>Results: </strong>Mice with chronic pain exhibited deficits in social preference and novelty. <i>In vivo</i> calcium imaging revealed that, during social interaction under pain conditions, the activity of ACC GABAergic neurons was reduced, whereas that of CaMKII⁺ neurons was increased. Chemogenetic manipulation demonstrated functional dissociation between these neuronal populations: activation of GABAergic neurons alleviated pain hypersensitivity but failed to rescue social deficits, whereas inhibition of these neurons improved pain-induced social deficits. Conversely, inhibition of CaMKII⁺ neurons attenuated hyperalgesia, while their activation partially restored social preference. Further analyses identified distinct interneuron subtype contributions, with parvalbumin-positive (PV⁺) neurons regulating both pain and pain-induced social preference deficits, and somatostatin-positive (SST⁺) neurons selectively mediating pain-induced social novelty deficits. These findings indicate that ACC neuronal subtypes exert complementary yet specialized roles in the comorbidity of pain and social deficits.</p><p><strong>Conclusions: </strong>Distinct ACC neuronal subtypes differentially regulate pain and social behaviors, revealing a functional \"conflict\" within the ACC whereby modulation of a single neuronal population cannot simultaneously ameliorate both pain and social deficits. These results underscore the necessity of circuit- and subtype-specific intervention strategies to disentangle and therapeutically target pain-related social deficit.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4619-4640"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378607","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":"Open Porous Microenvironment-regulatory Microspheres Loaded with Curcumin@BSA NPs/BMSCs for Diabetic Wound Treatment.","authors":"Zhe Liu, Qinzhou Zheng, Dong Zhou, Anqi Lin, Lan Xiao, Haifeng Liu, Keqin Ji, Huifen Qiang, Xinxin Sui, Yulin Li, Yan Wu, Jie Gao, Lan Liao, Xiaohuan Yuan","doi":"10.7150/thno.120285","DOIUrl":"10.7150/thno.120285","url":null,"abstract":"<p><strong>Background: </strong>The process of healing wounds in diabetic patients is intricate and is notably obstructed by a disordered wound microenvironment, characterized by chronic inflammation and elevated blood glucose. The combination of stem cell therapy and drug treatment is seen as a promising application in future. However, the limited proliferative capacity of stem cells and inadequate drug availability present significant challenges for achieving optimal therapeutic outcomes.</p><p><strong>Methods: </strong>In this study, open porous poly (lactic‒coglycolic acid) (PLGA) microspheres were designed and synthesized via gas-assisted volatilization microemulsion technology. These microspheres encapsulate curcumin and allow its slow release, thereby enhancing wound repair. The large pores in the microspheres provide ample support for bone marrow stem cells (BMSCs), enabling continuous drug release over a period of 35 days.</p><p><strong>Results: </strong>The sustained release of curcumin promoted stem cell proliferation and maintained stem cell activity. Additionally, it facilitates remodeling of the wound immune microenvironment. Additionally, the microspheres can activate mitochondrial autophagy in cells, effectively alleviating wound inflammation.</p><p><strong>Conclusions: </strong>The combined actions of curcumin and stem cells aid in regenerating blood vessels and revitalizing the collagen network where the injury occurred, thus improving wound healing capabilities. Consequently, integrating drugs with stem cells and microspheres holds significant potential for diabetic wound treatment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4521-4550"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378580","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":"Development of a dendritic cell-targeted vaccine strategy using proximity-induced conjugation.","authors":"Zhidong Wang, Xiaolin Yang, Jianjiang Li, Guang Chen, Haodi Ma, Zhengshuang Xu, Yu J Cao","doi":"10.7150/thno.122332","DOIUrl":"10.7150/thno.122332","url":null,"abstract":"<p><strong>Background: </strong>Traditional cancer vaccines that utilize peptides or proteins often exhibit limited efficacy as a result of mutations in cancer antigenic epitopes, also known as antigenic drift, which reduce the ability of traditional vaccines to target tumor antigens and elicit robust immune response.</p><p><strong>Methods: </strong>To address these challenges, we propose an innovative and universal strategy for dendritic cell (DC)-targeted neoepitope delivery via proximity-induced conjugation (PIC). This approach enables the site-specific crosslink of a broad spectrum of neoepitopes tailored to diverse cancer types, thereby increasing both vaccine flexibility and applicability. The PIC method involves the use of recombinant Fc-affinity peptides that are modified with two distinct unnatural amino acids: the photoreactive amino acid p-benzoyl-L-phenylalanine (pBPA) and the bioorthogonal reactive amino acid 4-fluorophenyl carbamate lysine (FPheK). These modified peptides allow for the precise conjugation of neoepitopes through ultraviolet (UV) irradiation or mild incubation, thereby achieving controlled antigen coupling.</p><p><strong>Results: </strong>Through optimization of this strategy, we observed a substantial increase in DCs mediated antigen uptake and processing, leading to enhanced T cell activation, a robust cytotoxic immune response, and significant improvements in antitumor efficacy. Moreover, the DC-targeted vaccine exhibited promising synergistic effects with an immune checkpoint inhibitor (ICI), resulting in a marked reduction in tumor growth and prolonged survival in preclinical models.</p><p><strong>Conclusion: </strong>These findings underscore the potential of the PIC-based DC-targeted vaccine system to augment the immunogenicity, versatility, and therapeutic efficacy of cancer vaccines. This strategy offers a compelling solution to the challenges posed by antigenic drift and mutation, thereby improving clinical outcomes across a broad range of cancers.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4641-4656"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378613","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":"Nanobiomaterial-enabled boron delivery systems and innovative strategies for revolutionizing BNCT.","authors":"Qiyao Yang, Ruxuan Wang, Huang Lingling, Qiong Bian, Qichun Wei","doi":"10.7150/thno.126209","DOIUrl":"10.7150/thno.126209","url":null,"abstract":"<p><p>Boron neutron capture therapy (BNCT) is a novel and emerging form of radiotherapy that combines the advantages of \"heavy ion radiotherapy\" and \"biological targeting\". The therapeutic potential of BNCT is ultimately constrained by precise and efficient delivery of boron drugs. In this review, we systematically trace from conventional boron drugs to sophisticated nano-delivery platforms, emphasizing breakthroughs in carrier engineering, targeted delivery strategies, and multifunctional synergistic systems. A dedicated analysis of the biological foundations, such as cell cycle dynamics, tumor microenvironmental interactions, and immunostimulatory effects, provides a crucial framework for understanding mechanism-informed biomaterial design. By synthesizing current advances with an outlook on future challenges, this work aims to chart a course for translating innovative boron-loaded biomaterials from the laboratory into clinical reality, thereby unlocking the full promise of BNCT.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4702-4725"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378623","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":"Blocking AREG-EGFR signaling attenuates pan-arterial fibrosis in chronic cardiac allograft rejection.","authors":"Kai Xing, Yuan Chang, Yuqi An, Xiao Chen, Xiaofei Zhu, Jian Huang, Peiyuan Li, Mengda Xu, Yixuan Sheng, Xingchao Du, Hao Liu, Jiangping Song","doi":"10.7150/thno.125318","DOIUrl":"10.7150/thno.125318","url":null,"abstract":"<p><strong>Background: </strong>Cardiac allograft vasculopathy (CAV) is a major barrier to long-term survival after heart transplantation, characterized by progressive vascular remodeling and luminal narrowing. Fibrosis is one of the key pathological features of CAV progression, but its underlying mechanisms remain unclear. This study aims to investigate the mechanisms of CAV-associated vascular fibrosis and explore potential therapeutic targets.</p><p><strong>Methods: </strong>Clinical specimens from the aorta (AO), pulmonary artery (PA), and coronary artery (CA) of CAV and control (Ctrl) groups were analyzed using single-cell RNA sequencing (scRNA-seq). Further validation was performed using a mouse arterial transplantation model.</p><p><strong>Results: </strong>This study found that vascular fibrosis occurs extensively in AO, PA, and CA, rather than being confined to CA alone. scRNA-seq analysis revealed that increased fibroblasts (FBs) and extracellular matrix (ECM) remodeling are common features across all three vascular regions. Cell-cell interaction analysis showed that T cells promote FB activation via AREG-EGFR. Two murine transplantation models further confirmed that blocking AREG-EGFR signaling significantly reduces fibrosis.</p><p><strong>Conclusion: </strong>Pan-arterial fibrosis represents a unifying pathological process across major vascular territories in CAV. Targeting fibrotic remodeling may offer a promising adjunctive strategy to improve long-term graft outcomes.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4603-4618"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378651","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":"Bacterial vesicles-initiated <i>in-situ</i> spray-polymerized coating enables synergistic antibacterial-photothermal functionality for accelerating wound healing.","authors":"Dan Wang, Shuya Liang, Zhijuan Ai, Qian Kong, Dongming Xing, Zhenping Cao, Zhongmin Geng","doi":"10.7150/thno.126844","DOIUrl":"10.7150/thno.126844","url":null,"abstract":"<p><strong>Background: </strong>Although microbial therapies can address the harm to beneficial bacteria and microbiome balance caused by traditional antibacterial treatments in skin damage and infection, their pathogenic potential limits clinical application. Bacterial extracellular vesicles (BEVs) offer a safer alternative by targeting microbes and modulating immunity.</p><p><strong>Methods: </strong><i>Lactobacillus reuteri</i>-derived BEVs (LBEVs) are functionalized with Fe <b>³⁺</b> via electrostatic adsorption, and co-sprayed with pyrrole monomers onto wounds to initiate oxidative polymerization and then form conformal polypyrrole coatings (LBEVs-PPy). Thanks to the natural antibacterial activity of LBEVs, the LBEVs-PPy coating could inhibit the growth of pathogens efficiently. Furthermore, the mild hyperthermia induced by PPy's NIR-triggered photothermal activation significantly upregulates the expression of angiogenic regulators.</p><p><strong>Results: </strong><i>In vitro</i>, LBEVs effectively inhibited the growth of <i>S. aureus</i>, <i>E. coli</i>, and <i>S. epidermidis</i>, demonstrating potent antibacterial efficacy. Following mild hyperthermia (42 °C for 1 h), HUVECs showed elevated expression of angiogenic regulators, including <i>VEGFA</i> and <i>ANGPT1</i>. This treatment also activates HSP90/p-eNOS pathway in HUVECs, thereby accelerating angiogenesis. In a mouse model of skin damage and infection, LBEVs-PPy coating significantly accelerates wound healing through synergistic mechanisms that integrate the antibacterial activity of LBEVs and the photothermal effect of PPy.</p><p><strong>Conclusions: </strong>Our research developed an in-situ spray-polymerized coating integrating antibacterial and photothermal modalities, thus presenting a promising biotherapeutic platform for clinical wound management and tissue regeneration.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4566-4579"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378608","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 Interleukin-4 Application Promotes Functional Recovery and Reprograms Neuroinflammatory and Molecular Responses after Spinal Cord Injury in Rats.","authors":"Obada Taleb Alhalabi, Stefan Heene, Guoli Zheng, Raban Heller, Tim Schubert, Marcin Luzarowski, Xiaowei Zha, Johannes Walter, Lea Hansen-Palmus, Bahram Biglari, Xing-Jin Wang, Laura Ruebenacker, Thomas Skutella, Karl Kiening, Christian Patrick Schaaf, Sandro Manuel Krieg, Andreas Wilhelm Unterberg, Klaus Zweckberger, Alexander Younsi","doi":"10.7150/thno.123815","DOIUrl":"10.7150/thno.123815","url":null,"abstract":"<p><strong>Rationale: </strong>Traumatic spinal cord injury (SCI) initiates a cascade of local and systemic inflammatory events that exacerbate tissue damage, hinder regeneration, and impair functional recovery. Interleukin-4 (IL-4) is an anti-inflammatory cytokine that promotes M2-macrophage polarization, but its functional benefit in SCI and the underlying mechanisms remain incompletely defined. We evaluated whether systemic IL-4 therapy can enhance recovery and modulate neuroinflammation in a rat model of SCI, and examined the translational relevance of key cytokine signatures in human SCI.</p><p><strong>Methods: </strong>Female Wistar rats (n = 120) were randomized to sham surgery, SCI with vehicle, or SCI with IL-4 treatment. SCI was induced at T10 by clip contusion-compression; IL-4 (0.5 µg/kg) or vehicle was administered intraperitoneally twice daily for up to 7 days post-injury (dpi). Functional recovery was assessed with the Basso-Beattie-Bresnahan (BBB) scale, CatWalk XT gait analysis, and gridwalk testing. Spinal cords collected at 1, 3, 7, 14, and 28 dpi underwent immunohistochemistry, RNA sequencing, and proteomic profiling. Serum cytokines were quantified in rats by bead-based multiplex assays and compared with longitudinal cytokine profiles from SCI patients.</p><p><strong>Results: </strong>IL-4-treated rats demonstrated significantly improved BBB scores and multiple CatWalk XT gait parameters by 14 dpi versus vehicle. RNA-seq and proteomics identified upregulation of pathways related to axonogenesis, tissue repair, and reduced TNF-α-mediated pro-inflammatory signaling. Immunohistochemistry confirmed increased IBA1⁺/ARG1⁺ and IBA1⁺/CD206⁺ M2-macrophages, reduced IBA1⁺/iNOS⁺ M1-macrophages, smaller cystic cavity area, and higher APC⁺ oligodendrocyte counts in IL-4-treated animals. Serum profiling showed suppression of acute/subacute pro-inflammatory cytokine surges (1-7 dpi) with IL-4. In SCI patients, lower circulating levels of these cytokines were associated with better neurological outcomes.</p><p><strong>Conclusions: </strong>Repeated systemic IL-4 administration after SCI promotes functional recovery, shifts macrophage polarization toward a regenerative phenotype, reduces astrogliosis and oligodendrocyte loss, and suppresses systemic inflammation. Multi-omics integration together with patient data suggests IL-4 targets convergent pathways of neuroprotection and immune modulation, supporting its further development as a therapeutic candidate for SCI.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 9","pages":"4726-4744"},"PeriodicalIF":13.3,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378620","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}