TheranosticsPub Date : 2025-08-11eCollection Date: 2025-01-01DOI: 10.7150/thno.113517
Jingyi Li, Liang Feng, Lei Zhang, Weiguo Zhang, Yanting Zhang, Xiaoqin Liu, Qianqian Cai, Weiming Zhao, Gang Huang, Changlian Lu
{"title":"Saikosaponin D Mitigates Radioresistance in Triple-Negative Breast Cancer by Inducing MRE11 De-Lactylation via HIF1α/HDAC5 Pathway.","authors":"Jingyi Li, Liang Feng, Lei Zhang, Weiguo Zhang, Yanting Zhang, Xiaoqin Liu, Qianqian Cai, Weiming Zhao, Gang Huang, Changlian Lu","doi":"10.7150/thno.113517","DOIUrl":"10.7150/thno.113517","url":null,"abstract":"<p><p><b>Background:</b> Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, exhibits poor prognosis due to radiotherapy resistance. However, the underlying mechanisms and effective therapeutic agents remain elusive. <b>Methods:</b> We employed lactate/oxamate to assess DNA damage/repair in irradiated TNBC cell lines. Lentiviral vectors for MRE11/HDAC5 constructs and shRNA were used to explore lactylation via Western blot/Co-IP. TCGA data mining, tissue microarrays, proteomics-MS, and gene expression profiling were used to dissect Saikosaponin D (SSD)'s radiosensitizing mechanisms. Promoter luciferase assays and ChIP-qPCR were performed to map SSD-induced HIF1α binding sites on the HDAC5 promoter. <b>Results:</b> Elevated endogenous lactate in radioresistant TNBC cells promoted DNA repair via MRE11 Lys<sup>673</sup> lactylation, a critical modification conferring radioresistance. HDAC5 was identified as the key delactylase for MRE11 Lys<sup>673,</sup> validated by HADDOCK docking (hydrogen bond between MRE11 Lys<sup>673</sup> and HDAC5 Ser<sup>18</sup>) and Co-IP (HDAC5 overexpression reduced K<sup>673</sup> lactylation). TCGA and clinical tissue microarrays confirmed HDAC5 downregulation in TNBC. SSD inhibits the malignant phenotype of TNBC and enhances radiotherapy efficacy by inhibition on MRE11 lactylation via upregulating HDAC5. Mechanistically, SSD upregulated HIF1α to bind the HDAC5 promoter (-342bp to -20bp region) to activate its expression. <b>Conclusion:</b> Lactate-driven MRE11 Lys<sup>673</sup> lactylation mediates radioresistance, while SSD reverses this via HIF1α/HDAC5 axis activation. Our findings identify SSD as a radiosensitizer and HDAC5/MRE11 as potential therapeutic targets for TNBC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8935-8951"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081714","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":"Long-lasting microbubble-enhanced super-resolution ultrasound imaging unveils lymphatic activity in lymph node.","authors":"Jingyi Yin, Feihong Dong, Xiangui Zhang, Yuan Peng, Pengting Min, Jiabin Zhang, Shu Wang, Jing Fang, Jue Zhang","doi":"10.7150/thno.117971","DOIUrl":"10.7150/thno.117971","url":null,"abstract":"<p><p><b>Rationale:</b> As the central regulatory hub localized at the interfaces between the blood and lymphatic vascular system, lymph nodes play a pivotal role in maintaining immune homeostasis and coordinating responses to disease. Systematic evaluation of lymph node functional status holds significant clinical value. However, there are currently no established non-invasive imaging biomarkers capable of reliably evaluating lymph node activity. <b>Methods:</b> This study developed a novel lipid-based long-lasting microbubble contrast agent (SuperVue-MB) integrated with three-dimensional super-resolution ultrasound (SRUS) imaging to achieve multiparametric hemodynamic visualization of blood vessels within lymph nodes. <b>Results:</b> Experimental validation demonstrated strong correlations between SRUS-derived vascular parameters and established reference standards (<i>r</i> = 0.86, p < 0.01), including micro-CT angiography and histopathological markers, confirming the reliability and accuracy of the technique. Furthermore, this study introduces a new vascular subtyping strategy that systematically correlates these hemodynamic patterns with immune functional states. Specifically, the density and number of microbubble tracks associated with key vascular subtypes, exhibiting significant positive correlations with lymphatic vessel density (<i>r</i> = 0.91, p < 0.01). <b>Conclusions:</b> This study offers a promising noninvasive approach for evaluating immune activation within lymph nodes, while establishing a novel paradigm for surveillance of sentinel lymph node metastasis and immunotherapy response monitoring.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8857-8872"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081640","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}
TheranosticsPub Date : 2025-08-11eCollection Date: 2025-01-01DOI: 10.7150/thno.111807
Yan Chen, Sarah E Bounds, Neloy Kundu, James Regun Karmoker, Yin Liu, Dongin Kim, Jiyang Cai
{"title":"Role of MiR-204 in controlling metabolic functions of the subretinal microglia.","authors":"Yan Chen, Sarah E Bounds, Neloy Kundu, James Regun Karmoker, Yin Liu, Dongin Kim, Jiyang Cai","doi":"10.7150/thno.111807","DOIUrl":"10.7150/thno.111807","url":null,"abstract":"<p><p><b>Rationale:</b> MicroRNA-204 (miR-204) is one of the most abundant miRNA species in the retinal pigment epithelium (RPE) and RPE-derived extracellular vesicles (EVs). Knockout (KO) of miR-204 leads to dysfunction and degeneration of both the RPE and the retina. In addition to previously reported retinal pathologies, we observed the accumulation of lipid-laden subretinal microglia in miR-204 KO mice. This study aimed to identify potential molecular targets of miR-204 involved in microglia lipid processing and to determine whether RPE-derived EVs can improve the function of miR-204-deficient retinal microglia. <b>Methods:</b> Lipid accumulation in microglia was detected by staining with LipidTox, a fluorescent dye specific for neutral lipids, followed by either flow cytometry analysis or direct visualization on RPE/choroid flat mounts. MiRNA database and target prediction tools, such as miRWalk and TargetScan, were used to search for potential target genes of miR-204 in microglia. The identified target mRNA was validated with a miRNA reporter assay. RPE EVs were prepared from <i>ex vivo</i> cultured mice eye cups and administered via retro-orbital injection in miR-204 knockout (KO) mice. RPE integrity was assessed by ERG c-wave measurement. <b>Results:</b> KO of miR-204 resulted in the accumulation of neutral lipids in subretinal microglia. MiR-204 targeted the TGF-β receptor 2 gene in microglia. TGF-β markedly suppressed the expression of genes related to microglia lipid clearance. Eyes injected with RPE-derived EVs showed improved ERG c-wave responses compared to the fellow eyes injected with saline. <b>Conclusions:</b> This study supports that TGF-β/TGF-β receptor 2 regulates microglia lipid metabolism primarily by suppressing lipid clearance. By modulating TGF-β signaling, miR-204 in RPE-derived EVs likely enhances the lipid metabolic activities of subretinal microglia, which are crucial for the structural integrity and proper function of the outer retina and RPE. RPE-derived EVs and their delivery of miRNAs represent a potential therapeutic approach for treating retinal diseases, such as age-related macular degeneration, which involve dysregulated lipid metabolism in subretinal microglia.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8952-8963"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081717","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":"Nociceptive Neurons Promote Myeloid-Derived Suppressor Cell Mobilization to Alleviate Post-Stroke Neuroinflammation.","authors":"Lingxin Cai, Jiayin Zhou, Xinran Cao, Huaping Huang, Qin Xie, Haifeng Chu, Gao Chen, Lulu Jin, Zhengwei Mao, Feng Yan","doi":"10.7150/thno.119474","DOIUrl":"10.7150/thno.119474","url":null,"abstract":"<p><p><b>Background:</b> Bone marrow serves as a source and reservoir of immune cells and plays a critical role in central nervous system diseases. Nociceptive neurons are widely distributed in the bone marrow, but their post-infarction changes and immunological functions remain largely unexplored. <b>Methods:</b> A mouse model of middle cerebral artery occlusion (MCAO) and human skull bone marrow samples from stroke patients were analyzed. Calcitonin gene-related peptide (CGRP) signaling was manipulated via receptor knockout and targeted nanoparticle delivery. Immune responses were evaluated primarily through flow cytometry, immunofluorescence, and single-cell RNA sequencing. <b>Results:</b> Activation of nociceptive neurons after cerebral infarction promoted myeloid-biased hematopoiesis in the bone marrow and increased infiltration of myeloid cells into brain tissue, resulting in anti-inflammatory and neuroprotective effects. This regulatory mechanism was mediated by CGRP, which enhanced the proliferation and mobilization of downstream myeloid-derived suppressor cells (MDSC), ultimately improving stroke outcomes. To overcome the hypotensive side effects of CGRP, we employed aged neutrophil membrane-coated nanoparticles for its targeted delivery to bone marrow, achieving sustained release and enhanced efficacy. <b>Conclusion:</b> Nociceptive neurons critically modulate post-stroke bone marrow immune responses by releasing CGRP and activating MDSC. Targeted CGRP delivery to bone marrow represents a promising strategy to suppress neuroinflammation and improve neurological recovery after cerebral infarction.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8897-8915"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081666","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}
TheranosticsPub Date : 2025-08-11eCollection Date: 2025-01-01DOI: 10.7150/thno.119712
Ningning Wang, Weizhen Li, Tuo Yang, Baolong Li, Chuikai Meng, Xiongyao Zhou, Jialu Sun, Kaiming Yu, Shusen Cui, Rangjuan Cao
{"title":"Targeting CB1R Rewires Ca<sup>2+</sup>-Dependent Mitophagy to Promote Nerve Regeneration.","authors":"Ningning Wang, Weizhen Li, Tuo Yang, Baolong Li, Chuikai Meng, Xiongyao Zhou, Jialu Sun, Kaiming Yu, Shusen Cui, Rangjuan Cao","doi":"10.7150/thno.119712","DOIUrl":"10.7150/thno.119712","url":null,"abstract":"<p><p><b>Background:</b> Ion homeostasis is disrupted following nerve injury, and elevated Ca<sup>2+</sup> levels have been reported to induce Schwann cell (SC) death. Notably, clinical interventions such as electrical stimulation enhance Ca<sup>2+</sup> influx and facilitate nerve regeneration. These findings highlight the need to clarify the precise role of Ca<sup>2+</sup> signaling in nerve regeneration. <b>Methods:</b> We assessed extracellular Ca<sup>2+</sup> concentrations in both human and murine peripheral nerve tissues after injury. Transcriptomic profiling identified CB1R as a key Ca<sup>2+</sup>-related gene and <i>in vitro</i> validation was performed with primary cultured SC and nerve explants. A sciatic nerve crush model was established in SC-specific CB1R knockout mice. Mitophagy, cellular metabolic homeostasis, and axonal regeneration were systematically assessed using proteomics, calcium imaging, and <i>in vivo</i> analyses. Additionally, the CB1R antagonist JD5037 was administered in both sciatic and optic nerve injury models to evaluate its translational potential. <b>Results:</b> Peripheral nerve injury (PNI) leads to elevated extracellular Ca<sup>2+</sup> levels at the injury site, where a moderate increase (~1.5-fold) favors SC survival. PNI also induces upregulation of CB1R, genetic ablation of CB1R enhances Ca<sup>2+</sup> influx, promotes SC survival, and maintains metabolic homeostasis. Mechanistically, CB1R interference upregulates adenine nucleotide translocase 2 (ANT2) expression, promotes mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane depolarization, thereby activating PINK1/Parkin-mediated mitophagy. This process improves mitochondrial quality and enhances energy metabolic efficiency, ultimately promoting axonal regeneration and functional recovery. Furthermore, systemic administration of the CB1R antagonist JD5037 similarly enhances regeneration of both peripheral and optic nerves <i>in vivo</i>. <b>Conclusion:</b> Moderate extracellular Ca<sup>2+</sup> elevation establishes a pro-regenerative microenvironment after nerve injury. Targeting CB1R facilitates Ca<sup>2+</sup> influx, enhances mitophagy via the PINK1/Parkin pathway, and promotes nerve regeneration. These findings identify CB1R as a viable therapeutic target and support the translational potential of JD5037 for nerve injury treatment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8873-8896"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Injectable SF-platform orchestrates GPX4-targeted ferroptosis-autophagy-immunogenic circuit for overcoming oxidative resistance in triple-negative breast cancer.","authors":"Hui Yuan, Xiongwu Li, Muhua Yu, Youde Cao, Lingcheng Wu, Suyujie Shi, Yaying Yang, Kexiao Yu, Bing Liang","doi":"10.7150/thno.116013","DOIUrl":"10.7150/thno.116013","url":null,"abstract":"<p><p><b>Background:</b> Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by the absence of targeted therapies and poor clinical outcomes. The development of novel, effective therapeutic strategies is urgently required to improve patient prognosis. Ferroptosis, a regulated form of cell death, has recently emerged as a promising therapeutic approach for TNBC. <b>Objectives:</b> This study aims to evaluate the efficacy of an injectable silk fibroin (SF)-based platform in treating TNBC and to explore the underlying mechanisms involved. <b>Methods:</b> We engineered an injectable SF platform consisting of magnetic, thermoresponsive silk fibroin-based hydrogels (IMSFs) coupled with temporally controlled TAT-Beclin1 delivery. Ferroptosis induction was quantified using the C11-BODIPY probe and transmission electron microscopy (TEM). To investigate the molecular mechanisms, RNA sequencing, Western blotting, and co-immunoprecipitation were performed. Additionally, enzyme-linked immunosorbent assay (ELISA) and flow cytometry were used to assess immune responses. <b>Results:</b> In the presence of an alternating magnetic field (AMF), IMSFs induce localized hyperthermia (42-45 °C) and catalyze Fenton reaction-driven reactive oxygen species (ROS) generation through Fe²⁺/Fe³⁺ release. The resulting ROS synergize with sorafenib release to inhibit the Xc⁻ system via the AMPK-Beclin1-SLC7A11 axis, leading to the local suppression of glutathione peroxidase 4 (GPX4) activity and the initiation of a ferroptosis cascade. Temporal delivery of TAT-Beclin1 prevents premature activation of autophagy, which could otherwise dampen ferroptosis. Instead, this approach leverages autophagy-ferroptosis synergy to amplify immunogenic cell death (ICD). This, in turn, activates CD8<sup>+</sup> T cells, triggering interferon-gamma (IFN-γ)-mediated downregulation of SLC7A11 and establishing a self-amplifying cascade of \"ferroptosis-autophagy-immunity\" loop that induces oxidative stress and leads to enhanced anti-tumor effects. <b>Conclusion:</b> The injectable SF platform, incorporating sequential therapeutic modules, demonstrates potent anti-tumor efficacy and holds significant promise for clinical translation in the treatment of TNBC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8757-8778"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081561","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":"Modulating Macrophage Polarization for Severe Acute Pancreatitis Therapy via Cisplatin-like Prussian Blue Nanozymes.","authors":"Ling Wu, Rui Cai, Yuhang Li, Shuqi Liao, Yinghui Song, Yufeng Li, Jishan Li, Donghong Yu, Zhong Cao, Sulai Liu","doi":"10.7150/thno.113523","DOIUrl":"10.7150/thno.113523","url":null,"abstract":"<p><p><b>Rationale:</b> Development of reactive oxygen species (ROS) antioxidants with high biosafety and anti-inflammatory properties for macrophage regulation in severe acute pancreatitis (SAP) therapy remains challenging. Here, we engineered a cisplatin-like calcium hexacyanoferrate Prussian blue nanozyme (Cri-Pt-CaFe<sub>PB</sub>) that functioned as a ROS scavenger to modulate macrophage polarization. <b>Methods:</b> The Cri-Pt-CaFe<sub>PB</sub> was prepared using a stepwise freeze-thaw method, and its structure and long-term stability were characterized by transmission electron microscope and dynamic light scatting. Subsequently, <i>in vitro</i> experiments were conducted to investigate the cytotoxicity and protective effects of Cri-Pt-CaFe<sub>PB</sub>. Fluorescence imaging and ICP-MS were applied to monitor its biodistribution and pharmacokinetics <i>in vivo</i>. Moreover, the biochemical kits, immunofluorescence, hematoxylin-eosin staining, and western blot were utilized to clarify <i>in vivo</i> therapeutic effect of Cri-Pt-CaFe<sub>PB</sub> in SAP mice. <b>Results:</b> Pt(VI) precursor was covalently coordinated with ultramicro CaFe<sub>PB</sub> nanospheres (~5 nm) and then converted into Pt(II) cisplatin-like nanozyme-based antioxidants, exhibiting exceptional ROS scavenging and anti-inflammatory effects at cellular and molecular levels with no toxicity <i>in vitro</i> or <i>in vivo</i>. Density functional theory simulation reveals the key role of Cri-Pt-CaFe<sub>PB</sub> with high peroxidase activity to the anti-inflammation treatment. Remarkably, the Cri-Pt-CaFe<sub>PB</sub> can protect the pancreas from oxidative stress damage and induce M1 to M2 macrophages repolarization after intravenous administration by downregulating CD86 protein expression (an M1 marker) and activating Arg-1 protein (an M2 marker), effectively reversing inflammatory damage in SAP and inhibiting the expression of proinflammatory cytokines. <b>Conclusions:</b> This study highlights the feasibility of Cri-Pt-CaFe<sub>PB</sub> nanozymes as ROS scavengers to regulate macrophage polarization towards M2 phenotype, which offers a novel effective nanomedicine strategy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8916-8934"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081623","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}
TheranosticsPub Date : 2025-08-11eCollection Date: 2025-01-01DOI: 10.7150/thno.116184
Dawei Wang, Wei Xu, Yuxin Liu, Luying Chen, Ting He, Hong Tan, Shuting He, Jie Zhu, Caiting Wang, Zhongyang Yu, Chong Li, Weidong Pan, Wei Rao, Jing Liu
{"title":"Liquid Metal Gallium Pharmaceuticals.","authors":"Dawei Wang, Wei Xu, Yuxin Liu, Luying Chen, Ting He, Hong Tan, Shuting He, Jie Zhu, Caiting Wang, Zhongyang Yu, Chong Li, Weidong Pan, Wei Rao, Jing Liu","doi":"10.7150/thno.116184","DOIUrl":"10.7150/thno.116184","url":null,"abstract":"<p><p>The room temperature liquid metal gallium, as a multi-targeted pharmacologically active metallic element with long historical investigation, has shown great potential in the field of medicine, especially in antibacterial, anti-inflammatory, anticancer, osteogenesis, radio-pharmacology, molecular imaging and more emerging drug categories. However, diverse structures and physical/chemical compositions, complex interactions with living organisms, and insufficient mechanism interpretation, pose serious challenges for the clinical translation of gallium-based pharmaceuticals. This review systematically identified and described promising gallium-based pharmaceuticals, with emphasis on typical features, fundamental pharmaceutical activities, representative pharmaceutical formulations, and practical implementations, aiming to inspire innovative concepts for drug discovery and further investigation. Meaningfully, new insights into gallium-based liquid metals for screening pharmaceutical formulations are presented, which promise to bring broader strategies for enhancing the bioavailability, targetability, biocompatibility and pharmacological efficacy of active pharmaceutical ingredients (Ga(0)/Ga(III)). Besides, the unresolved challenges and future perspectives of these emerging gallium-based pharmaceuticals were also outlined, aiming to aid for future academic explorations and translational medicine of gallium-based pharmaceuticals. Overall, gallium-based pharmaceuticals with tremendous pharmaceutical formulations and pharmaceutical activities open up a huge scope great potential for future pharmaceutical engineering, which are promising to usher epochal metallodrug development with a series of breakthrough discoveries and pioneering technologies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8795-8821"},"PeriodicalIF":13.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081574","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}
TheranosticsPub Date : 2025-08-08eCollection Date: 2025-01-01DOI: 10.7150/thno.114459
Konstantina Amoiradaki, Mateusz Tomczyk, Xiaoying Wang, Gastão Cruz, Carlos Velasco, Lorena Zentilin, Francesca Bortolotti, Claudia Prieto, René M Botnar, Mauro Giacca, Alkystis Phinikaridou
{"title":"Molecular and functional MRI enables detection of cardiac fibrosis and evaluation of treatment response after <i>chordin-like 1</i> gene therapy in myocardial infarction.","authors":"Konstantina Amoiradaki, Mateusz Tomczyk, Xiaoying Wang, Gastão Cruz, Carlos Velasco, Lorena Zentilin, Francesca Bortolotti, Claudia Prieto, René M Botnar, Mauro Giacca, Alkystis Phinikaridou","doi":"10.7150/thno.114459","DOIUrl":"10.7150/thno.114459","url":null,"abstract":"<p><p>Cardiac fibrosis (CF), characterised by accumulation of collagen and elastin, drives adverse cardiac remodelling and heart failure after myocardial infarction (MI). Currently, there are no non-invasive imaging methods to sensitively and directly assess CF and evaluate treatment response and no regenerative therapies for patients with MI. We hypothesised that functional and molecular magnetic resonance imaging (MRI) of collagen and elastin can detect and measure cardiac fibrosis and changes in response to <i>Chordin-like 1</i> (Chrdl1) gene therapy after MI. <b>Methods:</b> MI was induced in mice by permanent occlusion of the coronary artery. Mice received adeno-associated vectors serotype 9 (AAV9) expressing Chrdl1 (AAV9-Chrdl1) or an empty polylinker (AAV9-Control) by either intramyocardial injection, at the time of MI, or intravenous injection at 1 week post-MI. Mice receiving AAV9-Chrdl1 intramyocardially were imaged <i>in vivo</i> at 4 weeks after treatment. Animals treated intravenously were imaged before treatment, at 1 week post-MI, and again at 3 weeks after treatment. <i>In vivo</i> cine MRI at 3 Tesla was used to assess cardiac function. Molecular MRI was used to measure CF and treatment response using late gadolinium enhancement and T1 mapping after administration of collagen and elastin specific gadolinium probes. The imaging data were complemented by tissue analyses. <b>Results</b> MRI showed that intramyocardial treatment with AAV9-Chrdl1, immediately after MI, improved the ejection fraction (EF) (+48%) and decreased collagen (-62.1%) and elastin (-80%) fibrosis after 4 weeks of treatment compared with mice receiving AAV9-Control. Systemic administration of AAV9-Chrdl1 at 1 week post-MI, when CF was established and fibrogenesis was ongoing, effectively improved the EF (+6.9%) and reduced collagen (-42.1%) and elastin (-14.8%) fibrosis after 3 weeks of treatment. Conversely, in mice receiving the AAV9-Control the EF worsened (-30.7%) and CF increased (collagen +22.2% and elastin +40.8%). Changes in CF measured by MRI were validated by histology. <b>Conclusions:</b> This study shows the power of functional and molecular MRI to detect the therapeutic efficacy of Chrdl1 on cardiac fibrosis. Chrdl1 treatment inhibited the development and reduced existing collagen and elastin fibrosis resulting in improved cardiac function. This non-invasive image-guided theranostic strategy has the potential to accelerate the development of effective anti-fibrotic therapies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8706-8718"},"PeriodicalIF":13.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081581","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}