Theranostics最新文献

{"title":"Programmable pH-responsive DNA inter-strand matching (PRISM) for precision molecular band-pass actuation.","authors":"Xiaole Han, Hongyan Yu, Xiaomei Lin, Li Zhang, Weitao Wang, Yaoyi Zhang, Jianbo Jiang, Xingyu Liu, Ke Lv, Guoming Xie","doi":"10.7150/thno.136316","DOIUrl":"10.7150/thno.136316","url":null,"abstract":"<p><strong>Background: </strong>Precise sensing of narrow physiological pH ranges is important for accurate molecular regulation in complex biological environments. Traditional pH-responsive systems generally rely on monotonic off-to-on switching, making it difficult to distinguish subtle differences in tumor microenvironment pH (6.5-6.8) from neutral healthy tissues or highly acidic lysosomal compartments.</p><p><strong>Methods: </strong>We developed PRISM (pH-Responsive DNA Inter-Strand Matching), a universal and DNA-based strategy that functions as a programmable molecular band-pass filter. PRISM combines two antagonistic regulatory domains-an i-motif-mediated low-pH OFF module and a C-A mismatch-mediated high-pH OFF module-within a three strand framework. Through sequence-level thermodynamic design, the system defines a controllable operational window that enables non-monotonic molecular actuation.</p><p><strong>Results: </strong>Systematic characterization showed that PRISM generated band-pass signal responses with tunable operational range. The platform was successfully applied to high-contrast imaging of subtle pH gradients on HeLa cell surfaces, enabling effective discrimination of tumor microenvironment from both neutral and highly acidic environments. In addition, PRISM enabled allosteric regulation of fluorogenic DNA Lettuce aptamers and enabled logic gated control of CRISPR/Cas13a activity by integrating synthetic DNA modules with the intrinsic pH responsiveness of enzymes.</p><p><strong>Conclusion: </strong>Beyond conventional monotonic switching toward precise windowed regulation, PRISM offers a modular and biocompatible strategy for the development of intelligent theranostic platforms. This strategy facilitates high-fidelity diagnostic imaging and localized therapeutic activation within subtle pathological microenvironments without the need for complex bioconjugation.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7613-7625"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346349","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":"Engineering spherical nucleic acids for precision cancer therapy: design strategies and medical applications.","authors":"Yilin Wang, Wenbing Wu, Fuli Yao","doi":"10.7150/thno.132738","DOIUrl":"10.7150/thno.132738","url":null,"abstract":"<p><p>Malignant tumor treatment still faces issues like insufficient targeting, drug resistance, and immunosuppression. Spherical nucleic acids (SNAs), with their three-dimensional core-shell structure and densely packed, radially oriented oligonucleotide shell, enable transfection-free cellular uptake and provide nuclease resistance and stability. This review examines SNA engineering strategies and their impact on precision oncology. Functionalization with antibodies, aptamers, or antisense oligonucleotides enables SNAs to target key molecules such as human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and toll-like receptors (TLRs). Advances in stimuli-responsive, self-assembled, liposomal, and peptide-based carrier systems facilitate controlled drug release and modulation of the tumor microenvironment (TME). Diagnostic applications of SNAs include electrochemical, fluorescent, and colorimetric sensing systems for detecting biomarkers such as exosomes, miRNAs, alpha-methylacyl-CoA racemase (AMACR), and telomerase. Therapeutically, SNAs co-deliver chemotherapeutics and immunoadjuvants, support cancer vaccines, and exert efficacy in various tumors, including the central nervous, reproductive, digestive, hematological, barrier, and respiratory systems. Early clinical studies indicate a favorable biosafety profile, but issues remain regarding delivery efficiency, target selectivity, scalability, and long-term safety. Progress toward biodegradable, machine-learning-guided SNA platforms may soon make this nanotechnology a fundamental part of personalized, precision cancer medicine.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7466-7494"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346376","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":"Multimodal imaging-guided NIR-II photo-gas nanoplatform amplifies PD-1 blockade for synergistic TNBC therapy.","authors":"Linlin Song, Meixu Chen, Huiling Wang, Xin Wang, Tianyue Xu, Heqing Zhang, Shuwen Ran, Liwen Huang, Yingying Ma, Zhihui Liu, Zihan Xu, Yujie Zhao, Zichang Liu, Yong Luo, Xiujun Yu, Yulan Peng, Hubing Shi, Jing Jing, Xiujing He","doi":"10.7150/thno.133453","DOIUrl":"10.7150/thno.133453","url":null,"abstract":"<p><strong>Rationale: </strong>Triple-negative breast cancer (TNBC) remains one of the most aggressive subtypes due to its poor immunogenicity and resistance to systemic therapies.</p><p><strong>Methods: </strong>Here, we report a multifunctional NIR-II light-triggered theranostic nanoplatform, termed LQPO, that integrates liposome, Ti₃C₂ quantum dots (QDs), perfluorohexane (PFH), and ozone to enable multimodal imaging-guided photo-gas synergistic therapy. The QDs, embedded within the liposomal bilayer, act as highly efficient NIR-II photothermal transducers, while the PFH core serves as a liquid-gas phase-change medium capable of dissolving and releasing ozone under localized heating.</p><p><strong>Results: </strong>Upon NIR-II irradiation, LQPO produced strong photothermal and photoacoustic signals for real-time photoacoustic (PA) and contrast-enhanced ultrasound (CEUS) imaging, accompanied by vaporization of the PFH core and burst release of ozone. This spatiotemporally coordinated cascade induced potent oxidative stress and hyperthermia, synergistically driving GSDME-dependent pyroptosis and immunogenic cell death (ICD). The resulting \"in situ vaccination\" effect remodeled the tumor immune microenvironment and primed tumors for PD-1 blockade therapy. <i>In vivo</i>, NIR-II-activated LQPO achieved efficient tumor accumulation, strong PA/CEUS imaging contrast, and pronounced inhibition of both primary and abscopal tumors when combined with αPD-1 therapy. No significant systemic toxicity was observed, confirming its favorable biosafety.</p><p><strong>Conclusions: </strong>Overall, this study establishes a single-laser-activated nanoplatform that unifies real-time multimodal imaging and photo-gas synergistic therapy, and converts localized treatment into a systemic antitumor immune response upon integration with checkpoint inhibition.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7571-7593"},"PeriodicalIF":14.9,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346343","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":"Self-synergizing mutual prodrug liposomes for targeted cancer therapy <i>via</i> redox-amplified Pin1 inhibition.","authors":"Nuri Kim, Ilseob Kim, Hanui Jo, Nanhee Song, Sangmin Jo, Suyeon Lee, Hoechang Kim, Changjin Lim, Dongwon Lee","doi":"10.7150/thno.131597","DOIUrl":"10.7150/thno.131597","url":null,"abstract":"<p><strong>Rationale: </strong>Combination chemotherapy often suffers from poor pharmacokinetics, asynchronous drug delivery, and limited synergism. We anticipated that combining all-<i>trans</i> retinoic acid (atRA) with a quinone methide (QM) precursor would promote intracellular reactive oxygen species (ROS) accumulation through distinct yet complementary mechanisms. We further hypothesized that this redox disruption could ultimately suppress the oncogenic protein Pin1, resulting in synergistic anticancer effects.</p><p><strong>Method: </strong>We designed proxiRQ, a mutual prodrug in which atRA and a QM precursor are linked <i>via</i> an esterase-cleavable bond. Owing to the amphiphilic nature of proxiRQ, it was able to self-assemble with dipalmitoyl phosphatidylcholine (DPPC) to form cholesterol-free liposomes. We obtained tL-proxiRQ by further surface modification with poly(γ-glutamic acid) (γPGA), which improved systemic circulation and enhanced tumor accumulation. Subsequently, we evaluated physicochemical properties, esterase-triggered drug release, cellular redox modulation, and <i>in vitro</i> and <i>in vivo</i> antitumor efficacies.</p><p><strong>Results: </strong>tL-proxiRQ, featuring a high drug loading capacity (37 mol%) and colloidal stability, synchronously released atRA and QM upon esterase activation in tumor cells. QM-mediated glutathione (GSH) depletion amplified atRA-induced oxidative stress, thereby enhancing Pin1 expression inhibition. Compared to the free drug combination, tL-proxiRQ demonstrated significantly enhanced cytotoxicity, greater downregulation of Pin1, and enhanced apoptosis induction. <i>In vivo</i>, tL-proxiRQ achieved potent tumor growth inhibition in the MCF-7 xenograft model with minimal systemic toxicity.</p><p><strong>Conclusion: </strong>This study validates proxiRQ as a self-synergizing mutual prodrug and introduces tL-proxiRQ as a rationally engineered nanoplatform that integrates mutual prodrug chemistry, synergistic redox modulation, and targeted liposomal delivery to overcome the key limitations of conventional combination therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7442-7465"},"PeriodicalIF":14.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346412","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":"Ion-Responsive Microneedles Delivering Subtype-Specific Mitochondrial Extracellular Vesicles from HEY1⁺ Cardiomyocytes for Cardiac Repair in Bama Minipigs with Myocardial Ischemia-Reperfusion Injury.","authors":"Peng Qu, Jiao Shi, Xue Li, Yao Gu, Jun Liu, Hongyan Zhang, MingZhi Zhou, Cui Ma, Xinghui Li, Wenjie Tian, Qi Liang, Gang Li, Panke Cheng","doi":"10.7150/thno.123209","DOIUrl":"10.7150/thno.123209","url":null,"abstract":"<p><p>The pathogenesis of myocardial ischemia-reperfusion (MI/R) injury is intricately linked to mitochondrial dysfunction occurring during both the ischemic and reperfusion phases. Through single-cell transcriptome analysis, we identified a subpopulation of HEY1-high expressing cardiomyocytes (HEY1⁺ CMs) characterized by superior mitochondrial homeostasis. To leverage this, we isolated P5CS-type or ATP5B-type functional mitochondria from a ΔΨ_m-high subpopulation, which was obtained via membrane potential sorting following dual overexpression in HEY1⁺ CMs, and subsequently encapsulated them within HEY1⁺ CM-derived exosomes to achieve stable, targeted delivery. We designed a responsive microneedle patch based on local copper/iron ion dynamics to enable the stage-specific release of these mitochondria within the ischemic or reperfusion microenvironments. In a Bama minipig MI/R model, this system significantly ameliorated cardiac function, reduced infarct size, and attenuated cardiomyocyte death. Mechanistically, the therapeutic strategy enhanced mitochondrial structural integrity and energy metabolic function. This study establishes a responsive, stage-specific mitochondrial delivery platform, offering a promising strategy for the precision treatment of ischemic heart disease.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7367-7387"},"PeriodicalIF":14.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346374","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":"Engineered CCR2 positive macrophages coordinate immunoregulation with neural regeneration and matrix remodeling after spinal cord injury.","authors":"Yuqi Zhao, Tao Xie, Yanming Ma, Yuhao Wang, Shenghang Liu, Hui Li, Youjun Liu, Renfeng Liu, Hailiang Xu, Cheng Ju, Weidong Wu, Yifan Wang, Siyuan He, Rongjin Luo, Dageng Huang, Shuaijun Jia, Chunping Hu, Liang Yan, Zhiyuan Wang, Lei Zhu","doi":"10.7150/thno.134560","DOIUrl":"10.7150/thno.134560","url":null,"abstract":"<p><strong>Rationale: </strong>Spinal cord injury (SCI) triggers a complex secondary injury process characterized by inflammation, neuronal loss, extracellular matrix (ECM) disruption, and limited endogenous repair. Although cell-based therapies hold potential for SCI treatment, their efficacy is often constrained by poor lesion targeting, inadequate persistence after delivery, and limited temporal control over therapeutic factor release.</p><p><strong>Methods: </strong>To address these limitations, we developed a macrophage-based mRNA delivery platform by electroporating CCR2 positive (CCR2⁺) macrophages with ANXA1, GDNF, and CTGF mRNAs. <i>In vitro</i>, we assessed transfection efficiency, cell viability, secretion kinetics of therapeutic proteins, anti-inflammatory activity, and neuroprotective and regenerative effects. <i>In vivo</i>, using a mouse SCI model, we evaluated lesion-site accumulation, inflammatory regulation, tissue repair, electrophysiological recovery, transcriptomic alterations, and behavioral outcomes.</p><p><strong>Results: </strong>Following electroporation, CCR2⁺ macrophages efficiently expressed ANXA1, GDNF, and CTGF while maintaining high viability, with no marked shift toward CD86- or CD206-associated phenotypes. These engineered macrophages showed enhanced accumulation at the lesion site and sustained therapeutic protein secretion for up to 14 days. <i>In vitro</i>, they protected neuronal cells against oxidative stress-induced injury and promoted neurite outgrowth. <i>In vivo</i>, they attenuated inflammation, improved the local repair microenvironment, and promoted axonal regeneration, remyelination, and ECM remodeling, accompanied by partial recovery of electrophysiological and motor function after SCI. RNA-seq analysis further supported broad changes in pathways related to immune regulation, neural repair, myelination, and matrix remodeling.</p><p><strong>Conclusions: </strong>CCR2-enriched macrophages engineered with reparative mRNAs may represent a promising treatment strategy for SCI. By linking CCR2-associated lesion accumulation with multimodal reparative activity, this cell-based platform provides a potential approach for coordinated microenvironmental regulation and tissue repair.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7388-7418"},"PeriodicalIF":14.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346353","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":"Honeysuckle-derived nanovesicles alleviate inflammatory bowel disease-associated neuropsychiatric disorders via the gut-brain axis.","authors":"Ailin Wu, Qin Chu, Le Ding, Yan Zeng, Liqiang Shao, Yuanyuan Wang, Yuanhao Zhou, Weijiao Fan, Xin Zhang, Jianwei Wang, Jie Wang, Shunyuan Guo, Ketao Jin, Xiaoru Chang, Xiaozhou Mou","doi":"10.7150/thno.132241","DOIUrl":"10.7150/thno.132241","url":null,"abstract":"<p><strong>Rationale: </strong>Inflammatory bowel disease (IBD) is frequently accompanied by anxiety and depression, yet effective therapies targeting both intestinal inflammation and neuropsychiatric symptoms remain limited. This study aimed to investigate whether honeysuckle-derived nanovesicles (HNVs) could alleviate IBD-related affective disturbances by modulating the microbial-gut-brain axis (MGBA).</p><p><strong>Methods: </strong>A chronic colitis mouse model was established using dextran sulfate sodium (DSS). Mice were treated orally with HNVs, and anxiety- and depression-like behaviors were evaluated using behavioral assays. Intestinal barrier integrity, gut microbiota composition, systemic immune responses, proinflammatory cytokine production, hippocampal immune infiltration, 5-hydroxytryptamine (5-HT) biosynthesis and metabolism, and activation of the BDNF/TrkB/GSK3β signaling pathway were assessed using histological, microbiological, immunological, biochemical, and molecular analyses.</p><p><strong>Results: </strong>Oral administration of HNVs markedly attenuated anxiety- and depression-like behaviors in mice with chronic colitis. HNV treatment preserved intestinal barrier integrity, reshaped the gut microbial community, modulated systemic immune responses, reduced proinflammatory cytokine production and hippocampal inflammatory infiltration, and regulated 5-HT biosynthesis and metabolic pathways. These effects were associated with restoration of intestinal and neural homeostasis and activation of the BDNF/TrkB/GSK3β signaling cascade.</p><p><strong>Conclusions: </strong>HNVs alleviated IBD-related affective disturbances in experimental chronic colitis by regulating the MGBA, suppressing inflammation, modulating 5-HT metabolism, and restoring intestinal and neural homeostasis. These findings support HNVs as a potential natural nanotherapeutic strategy for the integrated management of intestinal inflammation and associated neuropsychiatric comorbidities.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7419-7441"},"PeriodicalIF":14.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346333","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":"Molecular design of MRI probes for targeting amyloid-β species: from <i>in vitro</i> binding to <i>in vivo</i> imaging.","authors":"Yupeng Shi, Ruiyang Zhang, Miaoqing Li, Yaning Xia, Mengyang Zhou, Rui Cao, Qing Zhou, Yong Zhang","doi":"10.7150/thno.131311","DOIUrl":"10.7150/thno.131311","url":null,"abstract":"<p><p>The aberrant aggregation of amyloid-β (Aβ) is a central pathological marker of Alzheimer's disease (AD) and shows different neurotoxic properties in various forms, such as monomers, oligomers, fibers and plaques. In recent years, great progress has been achieved in the molecular design and the development of magnetic resonance imaging (MRI) probes targeting Aβ species. They provide powerful tools for the early diagnosis and pathological investigation of AD. Here, we systematically review the molecular design strategies and recent advances in Aβ-targeted MRI probes. First, we introduce the molecular pathological basis of Aβ aggregation and the importance of Aβ as an imaging target. Second, we detail the core components of probe design, including the selection of targeting ligands (e.g., peptide mimetics, small molecules, and antibody fragments), optimization of signal units (e.g., Gd(III), Mn(II), superparamagnetic iron oxide nanoparticles (SPIONs), and ¹⁹F), and the delivery strategies to enhance blood-brain barrier (BBB) penetration. We focus on how the probes achieve the transition from high-affinity binding <i>in vitro</i> to high-contrast imaging <i>in vivo</i> by means of changes in proton relaxation times (T1/T2) or the chemical exchange saturation transfer (CEST) effect upon binding to Aβ. Furthermore, the imaging performance of various probes (small molecule probes, nanoprobes, and smart responsive probes) in transgenic AD models is compared and evaluated, and the challenges related to sensitivity, specificity, and biosafety are discussed. Finally, we discuss future directions for Aβ-targeted MRI probes, including oligomer-specific probes, multimodal imaging probes, and theranostic platforms that include both diagnostic and therapeutic functions. Through interdisciplinary innovation in molecular design, the next generation of MRI probes is expected to play a key role in preclinical research, early diagnosis, and therapeutic evaluation of AD.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7259-7287"},"PeriodicalIF":14.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346338","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":"Sonogenetics for precision medicine: from molecular toolkit to clinical translation.","authors":"Xinrui Yu, Min Pu, Ruoli Wang, Haitao Ran","doi":"10.7150/thno.134803","DOIUrl":"10.7150/thno.134803","url":null,"abstract":"<p><p>Sonogenetics is an emerging technology for precise biological modulation. It utilizes ultrasound waves for remote, noninvasive, and spatiotemporally precise functional intervention in target cells genetically engineered for acoustic sensitivity. This review systematically summarizes the three core components comprising sonogenetics: sound-responsive agents for modulating cellular functions, highly efficient vectors for targeted gene delivery, and ultrasound emitters with optimized parameters. Furthermore, we delineate optimization strategies for these components and propose a standardized workflow for sonogenetic operations. This review proposes strategies to accelerate the transformation process of sonogenetics by analyzing current limitations in regulatory efficiency and clinical safety. Finally, this review discusses the existing technical challenges and transformation bottlenecks, and points out the promising directions of future research.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7345-7366"},"PeriodicalIF":14.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345680","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":"P-glycoprotein 1 as a shared target for resensitizing drug-resistant tumor cells and preventing fibronectin-driven metastasis.","authors":"Li-Tzu Huang, Li-Hsin Cheng, Chin-Ho Kuo, Chin-Yun Cheng, Shane-Rong Sheu, Cheng-Han Yang, Pei-Chu Shih, Yi-Syuan Li, Lin Tseng, Wei-Ting Hsueh, Lyh-Jyh Hao, Hung-Chi Cheng","doi":"10.7150/thno.131375","DOIUrl":"10.7150/thno.131375","url":null,"abstract":"<p><strong>Rationale: </strong>The exacerbation of chemoresistance and metastasis by synthetic cytotoxic reagents hinders effective cancer therapy, as these events often coincide and lead to poor clinical outcomes, yet are rarely targeted through a shared molecular mechanism. To address this, we established a mechanism-informed natural compound discovery strategy to identify a non-cytotoxic candidate with dual functionality, namely re-sensitizing drug-resistant tumor cells and preventing metastasis.</p><p><strong>Methods: </strong>Western blot, RT-qPCR, and flow cytometry were used for evaluating protein and mRNA expression, as well as cell apoptosis, while GC/MS and HPLC analyses for identifying active phytochemicals from extracts of traditional Chinese medicines. Therapeutic potential was validated in multiple mouse cancer models, including K-ras^LSL-G12D/+; p53^fl/fl mice. Clinical relevance was investigated via meta-analysis of associated gene signatures.</p><p><strong>Results: </strong>Mulberroside A (Mul A) from <i>Cortex Mori Radices</i> was identified as an ideal compound that inhibits P-glycoprotein 1 (Pgp1) in adherent tumor cells and pericellular fibronectin (periFN) assembly on suspended tumor cells (STCs), which drive drug resistance and metastasis, respectively. Using a paclitaxel (PTX)-resistant Lewis lung carcinoma cell line, we demonstrated that ERK-dependent Pgp1 functions as a shared upstream regulator of both chemoresistance and metastatic competence. Accordingly, Mul A inhibited <i>Pgp1</i> mRNA and protein levels in an ERK-dependent manner, thereby differentially restoring PTX sensitivity both <i>in vitro</i> and <i>in vivo</i>, without intrinsic cytotoxicity, and significantly inhibiting lung metastasis by reducing the Pgp1-XIAP-periFN axis in STCs. Oral administration of Mul A achieved these dual anti-cancer effects in both experimental and spontaneous mouse models. Importantly, meta-analysis of clinical datasets further linked co-elevated <i>FN</i> and <i>Pgp1</i> expression with poor prognosis and relapse in early-stage cancer patients, underscoring the translational relevance of targeting this shared pathway.</p><p><strong>Conclusions: </strong>These findings identify Mul A as a promising non-cytotoxic therapeutic candidate and elucidate the shared upstream molecular mechanism linking distinct downstream chemoresistance and metastasis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"16 13","pages":"7288-7307"},"PeriodicalIF":14.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346409","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}