Theranostics最新文献

{"title":"Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.","authors":"Huifang Cheng, Hongyao Li, Peiyan Liu, Xin Jin, Yi Qu, Bo Liu, Aizhuo Li","doi":"10.7150/thno.134896","DOIUrl":"10.7150/thno.134896","url":null,"abstract":"<p><p>Recent advances in cancer neuroscience have established the nervous system as an active regulator of tumor initiation and progression, emphasizing the complex bidirectional crosstalk between neural networks and oncology. In order to deconstruct the relationship between primary central nervous system malignancies and brain metastasis, this review systematically studies the specific mechanisms of neuron tumor synaptic communication, paracrine signaling, and neuroimmune interactions. Innovatively, autophagy is considered as a regulatory bridge connecting neuronal activity and tumor behavior. When functioning in neurons, autophagic flux determines synaptic plasticity and regulates neurotransmitter turnover. Inside tumor cells, autophagy may lead to uncontrolled proliferation and help evade immune surveillance. Integrating these molecular observations establishes the neuro-autophagy-tumor axis, and interconnected nodes in this axis provide emerging therapeutic strategies that target neural signaling and autophagy. These insights highlight the importance of incorporating neurobiological context into cancer research and position autophagy as a promising target for disrupting neural regulation in cancer therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8077-8103"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680031","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 miniaturized-tumor culture platform for developing anti-tumor immunotherapies.","authors":"Yangyang Feng, Ling Li, Josh Haipeng Lei, Yuzhong Peng, Lijian Wang, Heng Sun, Dongyang Tang, Xinyu Guo, Xiangpeng Chu, Yunfeng Qiao, Kai Miao, Wen-Li Zhu, Chon-Wa Lam, Kin-Iong Chan, Wai-Kuok Chu, Shi-Xian Yao, Wei-Jian Hou, Xiaoling Xu, Zheng Chen, Chu-Xia Deng","doi":"10.7150/thno.132113","DOIUrl":"10.7150/thno.132113","url":null,"abstract":"<p><strong>Rationale: </strong>The preservation of the tumor immune microenvironment (TIME) <i>ex vivo</i> is essential for investigating tumor-immune interactions and developing effective immunotherapies. However, current culture models often fail to maintain autologous immune cells or support high-throughput testing. To overcome these limitations, we establish and validate a novel miniaturized-tumor culture (MTC) platform.</p><p><strong>Methods: </strong>To build the MTC platform, we took tumor tissues from both mouse models and human patients. We processed these tissues into 100-500 μm fragments. Supplementation with IL-2 and IL-7 in culture maintained long-term intra-tumoral T cell survival. We then evaluated whether the platform could maintain autologous lymphoid populations and respond to immune checkpoint blockade (ICB), through co-culture assays with peripheral blood mononuclear cells (PBMCs) or splenocytes. The system accurately recapitulates drug response and resistance in both immunocompetent and immunodeficient models. Finally, we screened a high-throughput drug library to identify agents that re-sensitize tumors to anti-PD-L1 therapy. To figure out the underlying mechanisms, we used bulk RNA-sequencing, flow cytometry, and targeted CXCL13 antibody neutralization.</p><p><strong>Results: </strong>The MTC platform demonstrated better preservation of autologous lymphoid populations and remained responsive to ICB. Co-culture assays revealed enhanced immune cell infiltration upon ICB treatment. Furthermore, the MTC models recapitulated drug response and resistance phenotypes. Our screen identified axitinib (AXI) as the most potent agent for re-sensitizing tumors to anti-PD-L1 therapy across different cancer types. Mechanistically, AXI potentiates antigen presentation in tumor and dendritic cells. It also enhances cytotoxic T-cell function via the upregulation of CXCL13. Finally, CXCL13 blockade effectively abrogated AXI-induced T cell recruitment and tumor regression.</p><p><strong>Conclusions: </strong>The MTC platform serves as a high-fidelity, high-throughput tool for modeling the TIME. It provides a valuable framework for developing novel anti-cancer strategies and elucidating their underlying mechanisms of action.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8129-8150"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680091","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":"Targeting microglial MyD88 reprograms injury-activated microglia and promotes spinal cord repair via TGF-β signaling and biomimetic nanodelivery.","authors":"Jintao Liu, Beibei Yu, Wanjun Cao, Jilu Liu, Yundi Gao, Honghui Mao, Xiaochuan Gao, Lingli Guo, Shengyou Li, Qiao Huang, Mingze Qin, Fang Kuang, Jinghui Huang","doi":"10.7150/thno.136733","DOIUrl":"10.7150/thno.136733","url":null,"abstract":"<p><strong>Background: </strong>Following spinal cord injury (SCI), activated microglia sustain neuroinflammation and drive secondary tissue damage, and this limits functional recovery. Myeloid differentiation primary response 88 (MyD88) is a central adaptor of innate immune signaling, but whether and how microglial MyD88 regulates state transition after SCI remains unclear. This study aims to explore the impact of microglial MyD88 signaling on microglial state trajectories and tissue repair after SCI and to develop a microglia-targeted delivery strategy for therapeutic modulation.</p><p><strong>Methods: </strong>A forceps-mediated SCI mouse model was established, and bulk and single-cell RNA sequencing were used to profile the temporal activation of microglial MyD88 signaling in the spinal cord. Pharmacological MyD88 inhibition (ST2825) and inducible microglia-specific MyD88 conditional knockout mice (<i>Tmem119</i> ^CreERT2;<i>Myd88</i> ^fl/fl) were used to assess neuroinflammation, tissue remodeling and downstream signaling. Functional recovery was evaluated by behavioral testing, bidirectional axonal tracing and electrophysiology. For translational validation, microglia membrane-coated, peptide-modified biomimetic nanoparticles (ST2825·DSPE@MG) were engineered to enhance microglia targeting and therapeutic efficacy.</p><p><strong>Results: </strong>Transcriptomic analyses revealed rapid and sustained activation of MyD88 signaling preferentially in microglia after SCI. ST2825 suppressed pro-inflammatory outputs <i>in vitro</i> and <i>in vivo</i> while preserving trophic mediators. Microglia-specific MyD88 deletion reprogrammed injury-activated microglia from a pro-inflammatory state to a repair-associated phenotype, reducing neuronal damage, preserving axons and improving locomotor recovery. TGF-β receptor blockade with LY2109761 abolished the protective effects of MyD88 deficiency. Additionally, ST2825·DSPE@MG nanoparticles exhibited microglia-targeted uptake and conferred superior therapeutic efficacy.</p><p><strong>Conclusion: </strong>Our data establish MyD88 as a critical regulator of microglial reprogramming after SCI and highlight its potential as a therapeutic target for spinal cord repair.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"8017-8035"},"PeriodicalIF":14.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679978","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":"Quantitative MRI Pharmacokinetic Modeling and MALDI Mass Spectrometry Imaging Biodistribution of a pH Mapping MRI Contrast Agent.","authors":"Zinia Mohanta, Caitlin M Tressler, Sadakatali Gori, Aruna Singh, Julia Stabinska, Shaowei Bo, Sana Karbalaei, Sophie Sall, Assaf Gilad, Hernando Lopez Bertoni, Eric Gale, Kristine Glunde, Michael T McMahon","doi":"10.7150/thno.128499","DOIUrl":"10.7150/thno.128499","url":null,"abstract":"<p><p>Chemical exchange saturation transfer (CEST) MRI enables noninvasive mapping of tissue pH, a key biomarker of renal physiology and disease. We report a streamlined, three-step synthesis of diGlu, an anionic imidazole-4,5-dicarboxamide bearing two glutamate substituents, obtained at ≥99.5% purity using SOCl₂/DMF activation, low-temperature amidation, and mild HCl deprotection-avoiding phenyl-ester intermediates and TFA. The molecule presents two exchangeable protons at 7.7 ppm (imidazole) and 4.5 ppm (amide) whose pH-dependent exchange rates enable a two-offset ratiometric, concentration-independent readout.</p><p><strong>Methods: </strong>C57BL/6J mice received tail-vein injections of 250, 500, or 750 mg kg^-1 I45DC-diGlu for our imaging studies. We established a novel biodistribution and pharmacokinetic analysis methodology employing matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) for biodistribution, CEST imaging and region of interest (ROI)-wise pharmacokinetic (PK) modeling, fitting SE (%) time-courses with log-normal (LN) and Uptake-Plateau-Decay (UPD) models and selecting the model by AICc on the SE time course curves.</p><p><strong>Results: </strong>MALDI-MSI confirmed selective renal localization and unmetabolized probe in urine, with negligible liver or pancreas accumulation. The LN model was best for fitting the CEST MRI data at low doses (unimodal kinetics), whereas UPD captured rise-hold-washout at 750 mg kg^-1, yielding interpretable biomarkers (SE_max, TTP, AUC_total, t_1/2). Robust renal CEST contrast was observed at ≥ 500 mg kg^-1. Voxel-wise pH maps reproduced the expected corticomedullary gradient (mean ± SD): cortex 6.86 ± 0.087, outer medulla 6.80 ± 0.073, inner medulla 6.61 ± 0.079, with pH estimates largely dose-independent.</p><p><strong>Conclusions: </strong>Together, the iodine- and metal-free chemistry, dual-offset window, dose-robust pH mapping, and MALDI-validated biodistribution position I45DC-diGlu as a practical scaffold for quantitative renal pH imaging and as a foundation for translational studies for renal pathophysiology.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7937-7957"},"PeriodicalIF":14.9,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679879","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":"PSMA-targeting hybrid molecule PSMA-914 for preoperative imaging and intraoperative fluorescence-guidance: A first-in-human experience.","authors":"Ann-Christin Eder, Mohamed A Omrane, Jessica Matthias, Sven Stadlbauer, Mareike Roscher, Kerstin Michalski, Martin A Schick, Christoph-Ferdinand Wielenberg, Peter Bronsert, Christian Gratzke, Martin Freitag, Klaus Kopka, Matthias Eder, Philipp T Meyer, Cordula A Jilg, Juri Ruf","doi":"10.7150/thno.129889","DOIUrl":"10.7150/thno.129889","url":null,"abstract":"<p><p>Surgery remains the cornerstone of prostate cancer treatment, demanding accurate tumor delineation and margin assessment. The hybrid molecule PSMA-914, which combines positron emission tomography (PET) and near-infrared fluorescence (NIRF) detection capabilities, was developed to improve preoperative imaging and intraoperative guidance during prostate cancer surgery.</p><p><strong>Methods: </strong>In this first-in-human series, prostate cancer patients underwent preoperative PET/CT imaging with ⁶⁸Ga-labeled PSMA-914 (n = 10), followed by fluorescence-guided surgery after intraoperative PSMA-914 administration (n = 7, doses ranging from 200 -1500 µg/patient). The optimal dose for effective tumor visualization was retrospectively evaluated, and both preoperative and postoperative imaging results were correlated with histopathological findings.</p><p><strong>Results: </strong>Preoperative PET/CT with [⁶⁸Ga]Ga-PSMA-914 showed high tracer uptake in primary tumors and metastases, facilitating accurate tumor localization. Intraoperatively, PSMA-914 at doses exceeding 1000 µg/patient provided a clear fluorescence signal, allowing for precise tumor and lymph node delineation. This approach significantly aided surgical resection by providing real-time guidance to differentiate malignant tissue from healthy tissue without altering the standard surgical workflow. Histopathological analysis confirmed the accuracy of [⁶⁸Ga]Ga-PSMA-914 PET/CT staging. The procedure was well tolerated without adverse effects.</p><p><strong>Conclusion: </strong>The dual modality of PSMA-914 has the potential to significantly advance prostate cancer surgery by combining diagnostic imaging and intraoperative guidance. These first results warrant further large-scale clinical trials to validate efficacy and safety across diverse patient populations. The integration of PSMA-914 into clinical protocols promises to benefit prostate cancer surgery by facilitating real-time, high-contrast visualization to aid in complete tumor resection.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7926-7936"},"PeriodicalIF":14.9,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679861","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":"Magnetic hyperthermia as an intracellular immunomodulatory technology: From heat transduction to tumor immune reprogramming.","authors":"Bin Yan, Lijun Dai, Hugang Li, Kexin Yuan, Huimin Yao, Lidan Chang, Haibin Peng, Xing-Jie Liang, Xiaoli Liu","doi":"10.7150/thno.130650","DOIUrl":"10.7150/thno.130650","url":null,"abstract":"<p><p>Magnetic hyperthermia (MH) has evolved from a localized thermal modality into an emerging intracellular immunomodulatory technology for cancer treatment. By employing magnetic nanoparticles (MNPs) to convert alternating magnetic fields into confined intracellular heat, MH enables precise spatial and temporal regulation of cellular stress responses while maintaining favorable biocompatibility and tumor selectivity. This review highlights recent advances that reposition MH as a cell-level immune regulation strategy, focusing on three interconnected aspects: (i) rational design of MNPs to optimize magnetic-to-thermal conversion efficiency and achieve precise intracellular heat transduction; (ii) integration of magnetic field-controlled MH with drug delivery and nano-heating modalities to enable synergistic intracellular regulation; and (iii) mechanistic insights into MH-induced immune modulation, including immunogenic cell death, immune cell activation, and its integration with tumor vaccines and cancer immunotherapy. Collectively, these advances establish MH as a versatile intracellular immunoregulatory platform and underscore its potential for precision cancer immunotherapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7897-7925"},"PeriodicalIF":14.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680110","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":"YOD1 drives acute kidney injury by deubiquitinating Bax and promoting apoptosis in tubular epithelial cells.","authors":"Ying Zhao, Shijie Fan, Yu Fang, Qingqing Zhao, Qian Zhou, Zheng Xu, Hong Zhu, Guang Liang","doi":"10.7150/thno.132208","DOIUrl":"10.7150/thno.132208","url":null,"abstract":"<p><strong>Rationale: </strong>Acute kidney injury (AKI) is a life-threatening clinical syndrome characterized by high mortality, in which tubular epithelial cell death represents a key pathological event. Emerging evidence underscores the importance of the ubiquitin system in the progression of AKI. Here, we focus on the function of YOD1 in AKI.</p><p><strong>Methods: </strong>We generated tubular epithelial cells (TECs)-specific <i>Yod1</i> knockout mice (YOD1CKO) by crossing <i>Yod1^fl/fl</i> mice and <i>Ggt1-cre</i> mice. Both YOD1CKO mice and <i>Yod1^fl/fl</i> littermates were subjected to cisplatin- or ischemia/reperfusion (I/R)-induced AKI models. Through co-immunoprecipitation (Co-IP) combined with LC-MS/MS analysis, we identified potential substrate proteins of YOD1.</p><p><strong>Results: </strong>We observed that YOD1 is predominantly expressed in TECs and is upregulated during AKI injury. Renal tubular specific <i>Yod1</i> knockout significantly alleviated tubular damage and apoptosis in AKI mice. Mechanistically, we identified the pro-apoptotic protein Bax as a direct substrate of YOD1. YOD1 removes K63-linked ubiquitin chains from Bax at lysine 128 via its catalytic cysteine residue C155, thereby promoting Bax activation, and mitochondrial translocation and subsequent apoptosis. YOD1 failed to promote apoptosis in Bax-deficient cells, confirming Bax as the essential downstream mediator.</p><p><strong>Conclusions: </strong>Our study reveals a previously unrecognized YOD1-Bax regulatory axis that drives tubular apoptosis in AKI, and highlights YOD1 may hold therapeutic potential.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7765-7779"},"PeriodicalIF":14.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679938","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":"Recent advances in targeting cyanine dyes: hierarchical targeting mechanisms and theranostic integration for multi-disease precision therapy.","authors":"Shuai Zhang, Yang Xu, Yu Wang, Zelin Chen, Yang Wang, Quanying Liu, Tantan Wang, Yali Dai, Chunmeng Shi","doi":"10.7150/thno.132719","DOIUrl":"10.7150/thno.132719","url":null,"abstract":"<p><p>The development of novel theranostic agents is a key initiative to address current limitations in disease diagnosis and therapy. Notably, targeting cyanine dyes (TCDs), by virtue of their excellent optical imaging performance, versatile structural modifiability, and multi-dimensional targeting specificity, facilitate the directional recognition of disease regions and exhibit tremendous application potential in theranostics. While a variety of TCDs have been successfully developed and their theranostic efficacy experimentally validated, researchers still lack a systematic summary of related studies. Although related advances in fluorescent probes, tumor theranostics, and NIR-II fluorophores have been reviewed, a focused and systematic overview of TCDs in terms of their synthesis, hierarchical targeting mechanisms, and multi-disease theranostic applications remains limited. Accordingly, this article systematically reviews TCDs' synthesis strategies, elucidates their \"tissue-cell-organelle\" hierarchical targeting mechanism, and summarizes the therapeutic applications in diseases including tumors, fibrotic diseases, metabolic diseases, and radiation-induced injuries. Compared with previous reviews, this review highlights the structure-inherent targeting properties of TCDs, their hierarchical targeting mechanisms, and their emerging theranostic potential beyond oncology. Meanwhile, this article outlines the core advantages and current challenges of TCDs in theranostic integration, and delineates key future directions, including precise and intelligent molecular design, photostability limitations, systematic preclinical evaluation, multimodal technology integration, and the expansion of disease application scenarios. It aims to provide comprehensive theoretical support for advancing the fundamental research and clinical translation of TCDs.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7869-7896"},"PeriodicalIF":14.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679887","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 role of an ultrasound-responsive injectable piezoelectric hydrogel in promoting nerve regeneration and alleviating neuropathic pain.","authors":"Zhaoyang Guo, Weiqian Jiang, Wentao Zhang, Zhongju Liu, Hang Zhou, Hang Liu, Lin Wang, Jiahao Zhang, Xinliang Peng, Xingyu Yang, Maohui Li, Hanchao Liang, Zhongyuan He, Rui Deng, Yongjun Dang, Wei Fu, Keyu Wei, Chao Xie, Zhong-Liang Deng, Youliang Ren, Lei Chu","doi":"10.7150/thno.131276","DOIUrl":"10.7150/thno.131276","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain (NP) resulting from peripheral nerve injury (PNI) represents a major clinical challenge. Although electrical stimulation (ES) has demonstrated therapeutic benefits, its clinical translation is limited by the invasiveness of electrode implantation, which often requires large surgical incisions and percutaneous wiring, increasing tissue damage and infection risk.</p><p><strong>Methods: </strong>This study developed an ultrasound-responsive, injectable, and biodegradable piezoelectric hydrogel (sPLLA-Gel) composed of electrospun poly-L-lactic acid (PLLA) and methacryloyl gelatin (GelMA). The physicochemical characteristics, biocompatibility, and piezoelectric performance were systematically evaluated. <i>In vitro</i>, ultrasound-activated sPLLA-Gel was examined for its ability to promote neural stem cell (NSC) differentiation and regulate macrophage polarization. <i>In vivo</i>, the hydrogel was injected into the sciatic nerve injury site of a chronic constriction injury (CCI) rat model, followed by behavioral, electrophysiological, histological, and transcriptomic analyses.</p><p><strong>Results: </strong>The sPLLA-Gel hydrogel exhibited excellent injectability, biodegradability, and ultrasound-induced electrical responsiveness. <i>In vitro</i> studies confirmed its biocompatibility and demonstrated that ultrasound-activated sPLLA-Gel promoted neural stem cell differentiation, axon-like neurite outgrowth, and favorable macrophage polarization. <i>In vivo</i>, the hydrogel was injected into the injury site of a chronic constriction injury rat model. Behavioral and electrophysiological analyses revealed that ultrasound-stimulated sPLLA-Gel enhanced myelin and axon regeneration, improved motor function, and alleviated NP. These therapeutic effects correlated with reduced spinal glial cell activation and decreased pro-inflammatory cytokine expression. Transcriptomic analysis and further validation suggested that sPLLA-Gel's analgesic and neuroprotective effects may arise from the inhibition of TRPV1 expression and the NF-κB signaling pathway.</p><p><strong>Conclusions: </strong>This study demonstrates the potential of this ultrasound-responsive piezoelectric hydrogel to promote peripheral nerve regeneration and mitigate NP, offering a promising minimally invasive strategy for treating sciatic nerve injury-related NP.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7780-7805"},"PeriodicalIF":14.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679989","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":"Illumination of Targeting Nanotherapeutics with Precision Eyes: From Optical to Radio-nanotheranostics.","authors":"Maharajan Sivasubramanian, Yao-Chen Chuang, Chia-Hui Chu, Yu Hsia, Li-Jie Lin, Leu-Wei Lo","doi":"10.7150/thno.130824","DOIUrl":"10.7150/thno.130824","url":null,"abstract":"<p><p>Cancer continues to rank among the deadliest diseases globally, claiming numerous lives due to its high mortality rates. Chemotherapy, a primary form of cancer treatment, offers significant benefits but is hampered by drawbacks that compromise patients' quality of life. Consequently, developing minimally invasive treatment alternatives remains a formidable challenge. Among these, nanomaterial-based, light-activated phototherapies-including photodynamic therapy, photothermal therapy, and radiotherapy-emerge as promising options, providing precise spatial and temporal control with reduced invasiveness. Advances in nanoscience and engineering have led to the creation of nanoparticles (NPs) that integrate therapeutic and diagnostic capabilities, known as theranostics, which enhance the effectiveness of clinical cancer management. This review summarizes recent advancements in nanotheranostics, spanning optical to radio-based approaches. We discuss the roles of various nanomaterials, such as upconversion NPs, gold NPs, nano-scintillators, and mesoporous silica NPs, among others, highlighting their dual diagnostic and therapeutic functionalities. Furthermore, NP-mediated induction of programmed cell death mechanisms-ferroptosis, pyroptosis, and cuproptosis-underscoring their significance in targeted cancer therapies and immune modulation were also explored. Additionally, we discuss how NPs can activate the stimulator of interferon genes pathway, amplify antitumor immunity and offer new avenues for improving cancer treatment outcomes.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 14","pages":"7806-7868"},"PeriodicalIF":14.9,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680023","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}