Circulating tumor cells (CTCs) are promising biomarkers for liquid biopsies in early cancer detection and monitoring, but their rarity and phenotypic heterogeneity make selective capture and non-destructive release challenging. Herein, we designed a novel DNA-inspired three-dimensional (3D) conjugating polymer-aptamer biointerface for selective capture and fringe-field pulsed electric field (FF-PEF)-triggered release of CEA-positive tumor cells. The platform was prepared by facile dip-coating a poly(para-aminophenol-co-thiophene) (PpAPT)-polyurethane (PU) blend onto a nonwoven carbon fabric (NCF) and was functionalized with carcinoembryonic antigen (CEA)-specific DNA aptamer to produce CEA/PpAPT-PU@NCF. The conjugated backbone and polar group (-OH/-NH2/-S-) functionalities of PpAPT, together with conductive fibrous 3D substrate, provided a hydrated and nucleic-acid-compatible interface for stable aptamer immobilization, low nonspecific binding and acceptable hemocompatibility. The CEA/PpAPT-PU@NCF composite exhibited high capture efficiency rate of 93% for CEA-positive HCT116 cells, with low nonspecific adhesion. More significantly, captured cells were released under optimized FF-PEF conditions, achieving up to 62.65% release efficiency through field-driven interfacial perturbation while preserving cell viability. These results demonstrate that CEA/PpAPT-PU@NCF provides a scalable platform for selective tumor-cell capture and non-destructive release, offering potential for liquid biopsy, downstream cellular analysis, and next-generation of bioelectronics applications.

[This corrects the article on p. 852 in vol. 13, PMID: 37034215.].

Table S1. Information on the sequences of shRNAs, sgRNAs, and siRNAs;Table S2. Information of sequences for primers; Table S3. Information of primary antibodies;Figure S1. Expression levels of AFDN in the GEO database; Figure S2. AFDN deficiency promotes CRC cells migration and invasion; Figure S3. Snail knockdown did not reduce CRC cells migration and invasion induced by AFDN deficiency; Figure S4. CXCR4 expression was increased in AFDN-deficient cells.

BACKGROUND:Local tumor progression and metastasis substantially compromise the therapeutic efficacy of thermal ablation in liver cancer. Although the inflammatory microenvironment contributes, the specific role of neutrophils after ablation remains unclear. This study aimed to clarify the roles of neutrophil extracellular traps (NETs) after thermal ablation and evaluate the translational potential of NETs-targeted strategies. METHODS:The adverse prognostic impact of thermal ablation-induced neutrophil and inflammatory changes in liver cancer was retrospectively evaluated. Circulating NETs were quantified by ELISA, and their association with local tumor progression was analyzed. An orthotopic liver cancer mouse model and patient-derived neutrophils elucidated the spatiotemporal dynamics and mechanisms of ablation-induced NETs, and pharmacologic inhibition was used to investigate NET formation, function, and translational potential. RESULTS:Thermal ablation rapidly activates neutrophils, elicits a sustained local inflammatory response and NET formation, which is closely associated with poor prognosis in patients with liver cancer. Depletion of neutrophils, inhibition of NET formation, or degradation of thermal ablation-induced NETs markedly suppressed post-ablation tumor progression. Mechanistically, tumor cell-intrinsic reactive oxygen species generated under heat stress contributed to nuclear factor kappa-B (NF-κB) activation, promoting p65 binding to theC-X-C motif chemokine ligand 1 (CXCL1) promoter and transcriptional upregulation of CXCL1. This process drove CXCL1-C-X-C motif chemokine receptor 2 (CXCR2) signaling and led to the formation of a characteristic band-like NETs-enriched zone at the peri-ablational margin. In turn, NETs activated toll-like receptor (TLR)9-dependent NF-κB,mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription 3 (STAT3) signaling in heat-stressed cancer cells, reinforcing a pro-inflammatory feedback loop. Concurrently, NETs impaired CD8+ T-cell responses and fostered an immunosuppressive microenvironment. Together, this coordinated pro-inflammatory and immunosuppressive effect promotes liver cancer progression following thermal ablation, which can be effectively reversed by dual blockade of NF-κB and CXCR2. CONCLUSIONS:Our research uncovers a novel mechanism underlying tumor-promoting inflammation after thermal ablation, highlighting the critical role of NETs as mediators through TLR9 activation of downstream inflammatory pathways and the significant potential of NETs-targeted strategies in combination with thermal ablation.

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of acute or chronic liver failure. It occurred in approximately 40% of acute liver failure cases and affected 30%-45% of patients with chronic liver failure or decompensated cirrhosis. Hyperammonemia is widely recognized as a central pathogenic factor in the pathogenesis of HE. Rifaximin (RIF), a non-absorbable oral antibiotic, was widely used to manage HE by modulating gut microbiota and reducing ammonia production. However, its clinical efficacy remained suboptimal due to poor aqueous solubility, limited dispersibility, and inadequate gastrointestinal retention. These limitations were further exacerbated in severe cases, owing to restricted oral dosing, recurrence associated with poor adherence, and potential risks of antimicrobial resistance and infection-related adverse events. This study presented a microalgae-nanoparticle hybrid system (SP@RIF) for drug delivery, in which RIF-encapsulated nanoparticles (RIFnano) were electrostatically loaded onto the surface of Spirulina platensis (SP), aiming to improve the oral delivery and therapeutic efficiency in HE treatment. RIFnano exhibited significantly enhanced antibacterial activity compared to free RIF. SP@RIF demonstrated prolonged gastrointestinal retention and sustained drug release profiles. In mouse models of HE, oral administration of SP@RIF markedly reduced systemic ammonia levels and improved behavioral outcomes. Furthermore, SP@RIF enhanced intestinal barrier function, attenuated systemic inflammation and neuroinflammation, ameliorated cognitive impairments, and modulated the gut microbiota. Importantly, these therapeutic benefits were achieved without observable toxicity. These findings highlight SP@RIF as a potential therapeutic strategy for treating HE.

Hepatocellular carcinoma (HCC) presents significant therapeutic challenges due to enhanced liver cancer stem cell (LCSC) stemness and sorafenib resistance after radiofrequency ablation (RFA). To address these limitations, biohybrid nanovesicles (hNVs) are prepared by fusing milk-derived exosomes with sorafenib-resistant LM3 cell membranes as nanovectors for targeted delivery of the HSP90 inhibitor alvespimycin (17-DMAG). The hNVs exhibit enhances tumor-homing capability through homologous targeting, achieving 3.2-fold higher tumor accumulation compared to unmodified exosomes. RFA of HCC significantly upregulates the expression of HSP90, leading to enhanced LCSC stemness and sorafenib resistance. In vitro and in vivo studies demonstrate that 17-DMAG loaded hNVs (17-DMAG@hNVs) effectively suppress LCSC stemness by downregulating HSP90 and its downstream signal pathways (TGF-β/Smad3 and JAK/STAT3), thereby restoring sorafenib sensitivity. Therefore, 17-DMAG@hNVs remarkably enhance the therapeutic efficacy of sorafenib after RFA of HCC. The reversal of LCSC stemness by inhibiting HSP90 expression using 17-DMAG@hNVs provides a promising approach to overcome sorafenib resistance for enhanced therapy of HCC after RFA.

Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to the limited efficacy of conventional treatments like surgery, radiofrequency ablation (RFA), and transarterial embolization (TAE). Here, we develop an innovative TAE and immunothermal therapy strategy based on smartly assembled near-micron layered double hydroxide particles co-loaded with STING agonist (NM-LDHs-cGP). By smartly responding to local charge fluctuations and microenvironmental changes, NM-LDHs undergo self-assembly and hierarchical stacking to form stable vascular embolic agents, thereby achieving superior embolization efficacy and excellent responsiveness to radiofrequency-induced thermal stimulation. NM-LDHs-cGP activates the cGAS-STING pathway, promotes dendritic cell maturation, and elicits robust CD8+ T and NK cell responses. Translational studies using human HCC tissues and immune cells confirm its ability to enhance RFA-induced cytotoxicity and trigger potent innate and adaptive immune activation. These findings establish smartly assembled NM-LDHs-cGP as a promising paradigm for combinatorial embolization-thermal ablation-immunotherapy in liver cancer.

Diabetic infected wounds heal poorly due to the synergistic effects of hyperglycemia, persistent microbial colonization, and chronic inflammation. We developed a pH-switchable artificial skin dressing TPI-PADL, to address these challenges. This system adapts to changes in the wound microenvironment over time. The dressing incorporates polydopamine and L-arginine modified PtAu nanozymes into a conductive ionogel-fiber scaffold. In the acidic and hyperglycemic conditions of early infection, the nanozymes exhibit glucose oxidase-like and cascade catalytic activities, increasing reactive oxygen species (ROS) production. The elevated ROS levels effectively kill bacteria and disrupt biofilms. As the wound environment shifts toward neutral pH, the nanozyme activity changes. The system begins to scavenge excess ROS and generate oxygen. The released oxygen reduces oxidative stress and improves local oxygen supply. These changes promote angiogenesis and guide macrophages toward a pro-healing phenotype. In vitro and in vivo evaluations confirm that TPI-PADL coordinates antibacterial, anti-inflammatory, antioxidant, and pro-regenerative effects. The ionogel network provides strain-sensing capability. This feature enables real-time monitoring of mechanical changes during healing. This strategy integrates therapy and sensing in a single platform for diabetic wound management.

Since the discovery of the cGAS-STING pathway, attempts to utilize it as an anti-tumor immunotherapy have attracted significant research interest and investment. However, relevant clinical translation remains hindered by immune evasion and systemic toxicity. We introduce BMSA, a first-in-class STING–PD-L1 heterobifunctional prodrug in which the PD-L1 inhibitor BMS-1 and the STING agonist MSA-2 are bridged by a tumor-cleavable linker. BMSA executes glutathione-triggered extracellular release of BMS-1 and intracellular esterase-mediated liberation of MSA-2, synchronizing dual immune signals at their respective sites of action. To confine activation to the tumor, we encapsulated BMSA into neutrophil-hitchhiking nanoparticles (T-NPs). After tail intravenous injection, T-NPs hijacked circulating neutrophils, accumulated at irradiated tumors via X-ray-induced inflammation, and exposed the fibrin-binding peptide CREKA through MMP-2/9 cleavage, producing markedly intratumoral accumulation while minimizing systemic exposure. This “Neutrophil–Tumor” cascade delivered heterobifunctional immunomodulation drugs with spatial and temporal precision, offering a translatable solution to the toxicity–efficacy dilemma that currently constrains STING-based cancer therapy.

Introduction In recent years, there has been a rise in the incidence of renal cell carcinoma (RCC), with metastatic RCC being a prevalent and significant contributor to mortality. While a regulatory role for microRNAs (miRNAs) in the development and progression of RCC has been recognized, their precise functions, molecular mechanisms, and potential clinical implications remain inadequately elucidated. Hence, this study aimed to explore the role of miR-507 in RCC and identify STEAP3 as a downstream target of miR-507.Methods Bioinformatics analysis was used to analyze the expression of miR-507 and STEAP3 in RCC specimens. CCK-8, Transwell, and flow cytometry assays were used to assess the function of miR-507 in RCC cells. The connection between miR-507 and STEAP3 was confirmed through a luciferase reporter assay. The expression level of STEAP3, p53, and xCT was analyzed by western blotting.Results Bioinformatics analysis showed that miR-507 was expressed at low levels in RCC tissues and was linked to poor overall survival. STEAP3 was found to be significantly upregulated in RCC. Further, STEAP3 was shown to be targeted by miR-507. High levels of miR-507 reduced the expression of STEAP3, leading to stagnant cell viability, apoptosis, and migrative capacity. Whereas miR-507 knockdown reverted such a tendency. The study also discovered that miR-507 exerted its inhibitory effect through the op53/xCT pathway.Conclusion Within RCC, miR-507 modulates the expression of SETAP3/p53/xCT axis, exhibiting a tumor suppressive effect. These discoveries offer present prospective biomarkers for both surveillance and treatment of RCC.

Irreversible electroporation (IRE) is a novel local tumor ablation technique that can potentially stimulate immune responses. However, IRE alone cannot effectively activate the immune system or prevent distant metastases. Therefore, this study utilized the biocompatibility of Chlorella vulgaris (C. vulgaris) and polydopamine (PDA) adhesive properties to encapsulate a PD-1 inhibitor (PI). The PDA coating protects the drug from degradation by stomach acid and enhances its intestinal absorption. This carrier demonstrates excellent in vivo drug release control and biodistribution, significantly increasing the oral bioavailability of PI. Combining IRE with this natural carrier significantly improves the therapeutic efficacy, which increases the local drug concentration and activates the immune system. This system demonstrates significantly improved therapeutic efficacy against local tumors compared with PI or IRE alone and significantly reduces PI-associated side effects. A convenient oral delivery system is developed using this readily available natural micro-carrier that not only improves the therapeutic effect of IRE but also mitigates its adverse effects, indicating significant potential for clinical applications. This discovery offers a new strategy for hepatocellular carcinoma treatment with the potential to improve patient outcomes.

Cancer cells reprogram the metabolism of glucose, lipids, and proteins (amino acids) to meet their energy needs during tumor initiation and progression. Amino acid sensing pathways play rucial roles in the progression and spread of colorectal cancer (CRC), but the crosstalk between these pathways and glucose and lipid metabolism has not been systematically elucidated. We summarize the roles of key amino acids in CRC, the corresponding nutrient sensors, the associated dysregulated signaling pathways, and their subcellular localization. Furthermore, we highlight how disrupted amino acid sensing forms an integrated regulatory network that modulates glucose and lipid metabolism through multiple signaling cascades. These insights reveal both opportunities for clinical translation and unresolved challenges in the field. We believe that this comprehensive review will stimulate further research in this emerging area and draw significant attention from both the scientific community and broader audiences. This review aims to identify new diagnostic markers, therapeutic targets, and prognostic indicators by enhancing the understanding of nutrient metabolic pathway interactions.

The development of biomaterials capable of capturing nondestructively capturing tumor cells is critical for advancing cancer diagnostics and personalized therapies. However, designing specific capture materials for maintaining the structure of captured cells is still a challenge due to the undesirable nonspecific adhesion. Recent evidence showed that neutrophils possess the tumor cell targeting property via the binding of β-integrin on neutrophil membranes to VCAM-1 expressed on tumor cells and natural antiadhesion properties due to the phosphorylcholine on the cell membrane. Herein, we present a neutrophil-inspired nanofibrous film for the nondestructive capture of tumor cells. The polyurethane and polyacrylonitrile (PU-PAN) blend film was fabricated by electrospinning as a matrix. A tailored zwitterionic polymer of poly-(sulfobetaine methacrylate-co-glycidyl methacrylate) (PScG), mimicking the phosphorylcholine on the cell membrane, was synthesized to graft onto the PU chain for preparing the PScG/PU-PAN film. Then, amino-modified aptamer (NH2-AS1411) targeting tumor cells, mimicking the β-integrin on neutrophil membranes, was further grafted onto hydrolyzed PAN surface to obtain the AS/PScG/PU-PAN film. The resulting AS/PScG/PU-PAN film demonstrates excellent specific capture ability of tumor cells, while maintaining the morphology of tumor cells, providing a promising solution for cancer therapy.

Hypoxia is a key driver of tumor environment restructuring, leading to gene expression profile variations in cancer cells. Increasing evidence has revealed hypoxia's initial action in epitranscriptomics, including RNA methylation. The role of tRNA-derived fragments (tRFs) in regulating tumor metastasis potential has attracted attention. Their expression in colon cancer cells under hypoxia was evaluated based on full-transcript sequencing and bioinformatic analysis. The transwell, loss-of-function, RNA immunoprecipitation-qPCR, artificial m5C modification, the dual luciferase reporter assay, and lung metastasis model assays were performed to explore the role of NOP2/Sun RNA methyltransferase 2 (NSUN2) and key tRFs in tumor progression. We found that the upregulated expression of tRFs (tRF ArgUCG) and downregulated expression of tRFs (tRF ArgCCG and tRF ArgCCU) in colon cancer cells under hypoxic conditions, both of which are derived from tRNA-Arg. Notably, our data identified C34 of tRNA-Arg as a key site that may play an essential role in the differential splicing of tRNA-Arg mediated by the methyltransferase NSUN2 under hypoxic conditions. We further studied the specific methylation of the tRNA Arg C34 site mediated by NSUN2 to protect tRNA from endonuclease cleavage and promote the metastasis of colon cancer cells in vitro and in vivo. In addition, TRIB1 was preliminarily identified as the target for tRF ArgCCG involved in colon cancer progression. In conclusion, our study offers a novel perspective on the molecular mechanism of methyltransferase NSUN2 regulating the selective expression of tRFs in colon cancer under hypoxic conditions.

The development of high-performance colorless polyimides (CPIs) demands a paradigm shift to overcome the mutual exclusivity of optical transparency, thermal stability, and mechanical strength. Drawing inspiration from nacre's hierarchical coordination motifs, a biomimetic strategy is presented that integrates molecular engineering with Zn2+-mediated crosslinking. Six pyridine-containing diamines are synthesized to suppress charge transfer complexes and copolymerized with 6FDA, forming tunable polyimide backbones. Subsequent Zn-2(+) coordination generates a dynamic N & horbar;Zn & horbar;N network, which rigidifies chains and delivers synergistic enhancements: an excellent T-g of 338.5 degrees C (+16.6%), ultralow charge transfer complexes of 45.8 ppm K--(1) (-20.6%), and tensile strength of 138 MPa (+46.8%) while retaining 89.3% transmittance. The film enable cytocompatible wearable sensors with 38 ms response times and stable signal output after 10 000 bending cycles. Moreover, its relevance to foldable ACEL devices highlights the potential for industrial scalability. This work reimagines CPI design through coordination chemistry, offering a blueprint for multifunctional polymers in next-generation electronics.

The morphological characteristics of tumor cells can provide valuable visual insights into the degree of cell differentiation, which is crucial for accurate cancer grading and diagnosis. The development of biomaterials that can selectively capture these cells while preserving their morphology is essential for advancing cancer diagnosis and treatment. However, designing anti-adhesion biomaterials that possess the ability to capture tumor cells and maintain their structure is still a challenge. Inspired by the dynamic interactions between extracellular matrix and cellular receptors, we propose a versatile nanofibrous membrane functionalized with aptamers and protein binding. Fabricated through a facile polydopamine (PDA) coating on a polyurethane (PU) membrane, this platform provides a bioactive surface for binding functional molecules. The covalent chemistry of PDA allows for the binding of streptavidin (SA) and bovine serum albumin (BSA), forming a highly hydrophilic BSA/SA/ PDA@PU membrane. Subsequently, a biotin-modified aptamer (AS1411), which specifically targets tumor cells, were further bound with SA to obtain the AS/BSA/SA/PDA@PU membrane. This modified membrane demonstrates high specificity in capturing tumor cells while preserving cell morphology, providing a promising approach for enhanced cancer diagnostics and therapeutic interventions.

Transarterial chemoembolization (TACE) serves as a locoregional therapy for hepatocellular carcinoma (HCC) patients. Nevertheless, the rapid dissociation of conventional TACE (cTACE) preparations, attributed to the instability of the emulsion, often leads to inadequate concentrations of chemotherapeutic agents within the tumor site. Consequently, there exists a pressing demand for an embolic agent that possesses facile injectability and the capacity to provide continuous delivery of chemotherapy drugs. Herein, we leveraged the inherent drug-loading capabilities and distinctive structural attributes of Spirulina platensis (SP) to formulate a novel microalgae embolic agent, doxorubicin loaded-Spirulina platensis (DOX-SP). The DOX-SP formulation exhibited a notable capacity for drug loading and demonstrated the ability to sustain drug release in response to acidic tumor microenvironments (TME). The spiral structure and micron-scale size of SP contributed to effective vascular embolization and continuous localized release of DOX. Furthermore, the biodegradability of SP as a natural biomaterial ensured good biosafety, with its degradation products potentially enhancing the pH of TME. In a rat model of in-situ hepatocellular carcinoma, DOX-SP effectively suppressed tumor growth and significantly reduced tumor size following intra-arterial injection, while exhibiting minimal adverse effects. Taken together, the high drug loading capacity, effective vascular embolization, pH sensitivity, TME pH modulation, and biodegradability of DOX-SP made it a promising embolic agent for hepatocellular carcinoma treatment.

Photodynamic therapy (PDT) is a promising cancer therapy modality by generating reactive oxygen species (ROS) and triggering immunogenic cell death. However, the therapeutic effect of PDT is strongly limited by tumor hypoxia and immunosuppressive landscape. Herein, a pH-sensitive nanosized covalent-organic polymer (COP), composed of the photosensitizer porphyrin and pyruvate kinase inhibitor vitamin K3 (VK3), is designed to overcome these issues. The signal transducer and activator of transcription 3 (STAT3) inhibitor WP1066 is further encapsulated into COPs to form a WP1066-loaded COP (TVW). As an inhibitor of pyruvate kinase, VK3 can reduce intracellular oxygen consumption by inhibiting the glycolytic pathway, leading to the alleviation of the tumor hypoxic microenvironment. The relief of tumor hypoxia by VK3 enhances photodynamic cytotoxicity by generating more ROS. Meanwhile, STAT3 acts as a major regulator of PD-L1, a key inhibitor that promotes immune escape. WP1066 effectively inhibits the expression of STAT3 and reduces PD-L1 expression, thereby significantly inhibiting tumor immune escape and enhancing antitumor efficacy in a synergistic manner. The antitumor capacity of photodynamic immunotherapy is extensively investigated in a murine subcutaneous hepatocellular carcinoma model. This photo-immunotherapy may provide an effective combination regimen for the efficient treatment of solid tumors such as hepatocellular carcinoma.

Incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC) has the risk to exacerbate the tumor immunosuppressive microenvironment and promote lung metastasis. There is an urgent need to reverse the immunosuppressive microenvironment and reduce lung metastasis after iRFA. Herein, an iron-based metal-organic framework loaded with capmatinib (Fe-MOF/Cap) is employed to reverse the immunosuppressive microenvironment dominated by M2-like tumor-associated macrophages (TAMs) after iRFA and inhibit lung metastasis of HCC. On one hand, Fe-MOF/Cap repolarizes M2-like TAMs to M1-like TAMs and inhibits the expression of PD-L1 after iRFA, promoting CD8+ T cell infiltration. The infiltration of CD8+ T cells and the decrease of PD-L1 are conducive to enhance the immunotherapy after iRFA. On the other hand, Fe-MOF/Cap can inhibit lung metastasis of HCC via inhibiting the expression of c-MET. In vitro and in vivo experiments confirm that Fe-MOF/Cap is able to significantly inhibit the lung metastasis of HCC after iRFA by inhibiting the c-MET/STAT3/VEGF pathway. Fe-MOF/Cap provides a potentially promising strategy for HCC immunotherapy and anti-metastasis after iRFA, with favorable clinical prospects.