Intervertebral disc degeneration (IVDD) is fundamentally driven by a self-perpetuating pathological loop involving metabolic derangement, oxidative stress, and enzymatic hyper-activity. Conventional mono-therapies often fall short of reversing this complex microenvironmental collapse. Here, we developed a smart nano-glycosphere (siMMP13/2-DG NPs) designed for dual-track intervention to restore disc homeostasis. This responsive platform utilized a 2-deoxy-D-glucose (2-DG) shell crosslinked via reactive oxygen-sensitive phenylboronic acid moieties, enabling the simultaneous suppression of pathological glycolysis and the neutralization of oxidative stress. Concomitantly, the precise delivery of siMMP13 effectively silenced major catabolic enzymes, thereby arresting extracellular matrix degradation. Our findings demonstrated that this combinatorial approach effectively interrupted the lactate-driven inflammatory cascade, shifting the microenvironment from a hostile catabolic state toward a pro-regenerative metabolic balance. In the lumbar disc degeneration model, the siMMP13/2-DG NPs significantly preserved structural integrity and alleviated discogenic pain by dampening neuro-inflammatory signaling. By integrating metabolic reprogramming with targeted gene silencing, this study establishes a versatile therapeutic paradigm for the precision management of IVDD and offers broader insights into the treatment of other microenvironment-mediated musculoskeletal disorders.

Annulus fibrosus defects disrupt the structural integrity and mechanical balance of the intervertebral disc, leading to nucleus pulposus herniation and subsequent nerve compression, which ultimately results in pain and related clinical symptoms. Therefore, developing biocompatible materials capable of effectively sealing annulus fibrosus defects is of great clinical significance for preventing nucleus pulposus extrusion and restoring disc function. In this study, we developed a wet-adhesive patch composed of silk fibroin-tannic acid adhesive integrated with a chitosan film (CS/SF-TA patch) for effective sealing of annulus fibrosus defects. The assembly of the SF-TA adhesive was driven by hydrophobic interactions and hydrogen bonding, enabling rapid gelation, strong wet adhesion, and self-healing capability. The CS/SF-TA patch achieved an interfacial adhesion strength with 71 kPa on wet porcine skin, while exhibiting antioxidative activity. In addition, the patch underwent swelling-mediated integration with surrounding tissues and demonstrates favorable biocompatibility. In vivo studies further showed that the composite patch effectively sealed annulus fibrosus defects, preserved nucleus pulposus hydration, and significantly attenuated disc degeneration. This polyphenol-mediated silk fibroin assembly strategy, combined with a chitosan substrate, provided a versatile platform for robust wet-tissue adhesion and may be extended to a wide range of biomedical applications requiring mechanically support and self-healing adhesive materials.

Oral ulcers remain difficult to treat owing to the mechanically dynamic and microbially rich oral environment, where constant shear forces, microbial challenge, and oxidative stress collectively impede mucosal repair. Here, we report a versatile injectable self-healing bioadhesive hydrogel sealant (F127-AG) based on dynamic Schiff-base crosslinking between aldehyde-modified Pluronic F127 (PF127-CHO) and amine-functionalized gelatin (AG), enabling rapid in situ gelation, strong wet tissue adhesion, and intrinsic self-healing. Kaempferol was incorporated into the hydrogel matrix, and the resulting Kae@FG hydrogel exhibited antioxidant and antibacterial activities. In vitro, Kae@FG exhibited excellent hemocompatibility and cytocompatibility, promoted fibroblast migration, and degraded favorably in artificial saliva. Additionally, it effectively scavenged reactive oxygen species and displayed potent bactericidal activity against both E. coli and S. aureus. In a rat oral ulcer model, Kae@FG accelerated wound closure, enhanced epithelial regeneration, improved collagen deposition, and promoted neovascularization, outperforming the commercial GENGIGEL®. Mechanistically, Kae@FG exerted an immunomodulatory effect by attenuating local inflammation, reducing neutrophil and M1 macrophage infiltration, and promoting M2 macrophage polarization, thereby supporting a pro-regenerative microenvironment. Overall, the F127-AG platform represents a versatile therapeutic delivery system with substantial potential for promoting regeneration of oral and other soft tissues.

The achievement of periodontal bone regeneration using a barrier membrane in guided bone regeneration (GBR) technology is often limited by either its inferior mechanical strength or bioactivity. To address this limitation, we developed a novel Janus bilayer membrane by sequentially electrospinning poly(ε-caprolactone) (PCL) mixed with proanthocyanidin (PCL-PA) and chitosan (CS) in acetic acid, then biomineralized it in simulated body fluid (SBF) to form hydroxyapatite particles (HAp) in situ on a CS nanofiber layer (CS-HAp): PCL-PA/CS-HAp. This bilayer membrane exhibited superior mechanical performance compared to single-layer membranes, with a peeling strength of 58 J/m2 and tensile strength exceeding 5.0 MPa under hydrated conditions. In vitro antioxidant assays demonstrated the strong free-radical-scavenging ability of PCL-PA/CS-HAp. In addition, the PA-incorporated membranes exhibited greater than 95% bacterial inhibition against both Gram-negative E. coli and Gram-positive S. aureus, and 90% against P. gingivalis. The bilayer membrane also alleviated oxidative stress induced by hydrogen peroxide (H2O2), thereby promoting the proliferation of MC3T3-E1 cells, as monitored by cytoskeletal staining. Flow cytometry analysis showed that the PA-incorporated membrane can stabilize immunomodulatory effects by about 10% in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. When used in a rat periodontal bone defect model, significant bone regeneration was observed in the PCL-PA/CS-HAp group, with a bone volume to total volume ratio of 36.2% and a significant reduction in bone defect size after 8 weeks, outperforming other treatment groups (p < 0.001). The PCL-PA/CS-HAp bilayer membrane represents a promising strategy for guided bone regeneration, effectively combining mechanical stability and bioactive properties.

Repair of oral soft-tissue injuries remains challenging due to the moist, bacteria-rich, and mechanically active oral environment, as well as the limitations of current sealants in wet adhesion, mechanical strength, biocompatibility, bioactivity, and sealing durability. Here, we report an injectable hydrogel sealant (PAG) composed of tetra-armed poly(ethylene glycol) succinimidyl succinate and amine-functionalized gelatin, which rapidly forms in situ via NHS-amine coupling without external triggers. The optimized formulation undergoes gelation within seconds and exhibits robust mechanical properties, as well as superior adhesive strength and burst pressure compared with commercial fibrin glue. PAG demonstrates excellent cytocompatibility, hemocompatibility, and biodegradability, while promoting fibroblast proliferation in vitro. In vivo, it enables rapid hemostasis within 3 s and effective tissue repair in an acute rat tongue perforation model, markedly outperforming suture, gelatin sponge, and fibrin glue controls. Moreover, PAG effectively protects early-stage wounds and accelerates repair in both rat and porcine oral mucosal defect models. Mechanistic studies indicate that PAG establishes a pro-regenerative microenvironment by attenuating excessive inflammation, enhancing angiogenesis, and promoting M2-dominant macrophage polarization. Collectively, these findings demonstrate that the engineered PAG hydrogel enables rapid, sutureless sealing and repair of oral soft-tissue wounds, highlighting its translational potential.

Watertight dural closure is essential for successful cranial and spinal surgery but remains a major clinical challenge due to persistent cerebrospinal fluid (CSF) leakage and associated complications. Conventional dural suturing is particularly challenging in cases involving fragile dura or anatomically complex defects, while existing sealants often suffer from delayed gelation, inadequate wet-tissue adhesion, and excessive swelling that may cause neural tissue compression. Herein, we report an injectable, biocompatible, low-swelling bioadhesive sealant (DLSS) based on N-hydroxysuccinimide-activated tetra-armed poly(ethylene glycol) and amine-functionalized gelatin for sutureless dural repair. The optimized hydrogel exhibits rapid in situ gelation, robust mechanical properties, effective wet-tissue adhesion, high burst pressure resistance, and limited swelling (13.2% volumetric swelling ratio in artificial CSF). Furthermore, DLSS demonstrates cytocompatibility and hemocompatibility, supports fibroblast migration, and undergoes controlled biodegradation. Ex vivo testing on rabbit dura demonstrated rapid and durable sutureless sealing of dural defects by DLSS. In vivo evaluation in rat cranial and spinal dural defect models demonstrated that DLSS enabled effective dural closure and tissue repair without detectable CSF leakage, showing improved performance compared with commercial fibrin glue. Its translational potential was validated in clinically relevant beagle models. Collectively, DLSS offers a promising strategy for sutureless dural repair.

The second near-infrared (NIR-II, 1000-1700 nm) window enables deep-tissue optical interrogation with high spatial resolution for biomedical applications, but molecular design is hampered by trade-offs among five parameters: absorption and emission wavelengths (lambda abs, lambda em), fluorescence quantum yield (QY), molar extinction coefficient (epsilon), and photothermal conversion efficiency (eta). Here, we report a molecular engineering strategy that balances radiative and nonradiative decay within an aggregation-induced emission (AIE) framework. We construct a benzobisthiadiazole (BBT)-based D-A-D-A-D-A-D chromophore, MTBTMT-BBT, comprising a rigid planar pi-core and twisted peripheral donors that yield an AIE-ACQ-AIE framework. In F127-encapsulated nanoparticles (MTBTMT-BBT NPs), this architecture affords increased NIR-II fluorescence quantum yield and sustained long-wavelength absorption/emission with high photostability, and retains strong absorption capacity (high molar extinction coefficient) together with efficient photothermal energy conversion under 808 nm irradiation. Spectroscopic analysis and calculations link the design to controlled aggregate packing that suppresses nonradiative decay yet preserves sufficient heat generation. In vivo, MTBTMT-BBT NPs enable high-contrast NIR-II vascular and tumor imaging and, upon laser irradiation, achieve complete 4T1 tumor eradication without recurrence or systemic toxicity, establishing a general design principle for Pareto-balanced NIR-II chromophores and multifunctional molecular theranostics.

Treatment of uncontrolled non-compressible hemorrhage remains challenging due to complex anatomical constraints and limitations of existing expandable hemostatic materials, which often lack sufficient porosity, mechanical robustness, biocompatibility, and capacity to support tissue regeneration. To address these issues, an injectable self-expanding hemostatic sponge was developed using a vacuum-assisted foaming strategy that harnesses bubble evolution to enlarge pores and enhance interconnectivity, with mechanical stability reinforced by a physically-chemically integrated double-network matrix. The optimized formulation (IHMS) exhibited hierarchically interconnected macroporous networks with excellent fatigue resistance, retaining 94.2% of peak stress and 92.7% of strain after 100 compression cycles at 80% strain. It outperformed commercial hemostatic sponges in fluid absorption, blood retention, clot formation, and tamponade sealing. Systematic evaluations demonstrated its intrinsic antibacterial activity, favorable biocompatibility, and ability to promote tissue repair. In rat liver perforation and femoral artery transection models, IHMS achieved superior hemostatic efficacy compared with cotton and commercial sponges. In lethal porcine hemorrhage models under normal and anticoagulated conditions, IHMS provided rapid and durable tamponade, outperforming the FDA-approved XSTAT, and could be easily removed after hemostasis. Its efficacy was further validated in junctional gunshot wound models. These findings advance the design of high-performance expandable hemostats for life-threatening non-compressible hemorrhage.

Abstract Developing biocompatible expandable hemostatic sponges that integrate rapid and high-capacity fluid uptake, mechanical resilience, and strong procoagulant activity remains highly desirable for the management of noncompressible hemorrhage in trauma care. Herein, a naturally derived injectable self-expanding γ-poly(glutamic acid)/carboxymethyl cellulose (γPGA/CMC) sponge was developed for noncompressible hemorrhage management. The sponge was fabricated through stirring-assisted foaming and further reinforced by a physical-chemical dual-network structure comprising covalent crosslinking of methacrylate-functionalized γPGA and Ca2+-mediated ionic interactions with carboxyl groups. Through systematic optimization of the formulation, the resulting γPGA/CMC sponge exhibited a highly interconnected porous structure with higher porosity, enhanced fluid absorption capacity, and improved procoagulant activity compared with commercial gelatin sponge and XSTAT. In addition, the sponge exhibited favorable biocompatibility and degradability. In rat liver perforation and femoral artery transection models, the γPGA/CMC sponge demonstrated significantly improved hemostatic efficacy compared with gelatin sponge and XSTAT. Furthermore, it effectively controlled severe bleeding in porcine liver and femoral artery injury models. Together, these results highlight the potential of the γPGA/CMC sponge for noncompressible hemorrhage management.

Background:Arthroscopic repair of osteochondral (OC) defects using injectable hydrogels remains highly challenging due to the high-pressure, water-filled environment of the joint during arthroscopic surgery. Conventional hydrogels exhibit slow gelation kinetics, prolonged setting times, poor adhesion to wet tissues, and insufficient mechanical strength, rendering them prone to washout throughout the procedure. Methods:To address these limitations, we incorporated a small amount of transglutaminase (TG) and synthetic lithium silicate nanoplatelets (SN) into a gelatin-oxidized starch (GelS) precursor and evaluated the regenerative performance of the resulting hydrogel under simulated arthroscopic conditions. In vivo, the hydrogels were implanted into osteochondral defects in rats to assess their repair efficacy. Results:The GelS-TG-SN hydrogel demonstrated ultrafast enzymatic gelation, robust underwater adhesion, and significantly enhanced mechanical strength. It was cytocompatible, displayed anti-inflammatory activity, and supported context-dependent dual-lineage differentiation of Synovial-derived stem cells (SDSCs) chondrogenesis in a cartilage-like niche and PI3K-Akt-mediated osteogenesis in a vascular-like niche. Following 8-week implantation, it enabled coordinated regeneration of cartilage and subchondral bone, recapitulating native osteochondral architecture. Conclusion:The GelS-TG-SN nanocomposite hydrogel offers a compelling strategy for effective osteochondral regeneration in arthroscopic surgical environments. The Translational Potential of this Article:This hydrogel platform offers an elegant and clinically accessible solution for arthroscopic osteochondral repair. Its ultrafast gelation-achieved in under one minute-combined with resilient adhesion under constant irrigation enables seamless intraoperative application without auxiliary instrumentation. By capitalizing on the body's intrinsic osteochondral gradient, a single injection orchestrates synchronized regeneration of cartilage and subchondral bone. Such integration of procedural simplicity with inherent regenerative bioactivity underscores its promise as a genuinely "one-step" therapy ready for clinical translation.

Engineered bacteria—microbial strains endowed with bespoke functionalities via genetic or protein engineering—represent a cornerstone of synthetic biology. These living diagnostics have shown immense potential across diverse sensing applications, including disease diagnostics, environmental surveillance, and food safety assessment. Recent advances in artificial intelligence (AI) have further propelled the field by enabling the efficient analysis of complex biological datasets, identification of nuanced signal patterns, and rational optimization of genetic circuits. In this review, we first summarize the fundamental design principles underpinning engineered bacterial biosensors, encompassing chassis selection, genetic circuit construction, and signal transduction modules. We then explore emerging roles of AI in component discovery, regulatory circuit refinement, and predictive modeling of system behavior. Representative case studies highlight the translational potential of these intelligent biosensors in real-world monitoring scenarios. Finally, we discuss key challenges—including biosafety, long-term stability, and regulatory hurdles—and propose future directions for the development and clinical implementation of AI-augmented engineered bacterial sensing platforms.

Meniscal injuries significantly impact knee function and pose clinical challenges globally. Conservative treatment and surgery are currently the more commonly used treatments, and there are still long-term joint problems such as incomplete meniscus healing and knee pain. Tissue engineering presents a promising alternative by using biomaterials, cellular therapies, and bioactive factors to repair meniscal damage. Despite the promising preclinical results, clinical applications still face challenges such as insufficient biomechanical strength, weak regenerative ability, or low durability. This review seeks to bridge clinical needs with engineering strategies by providing a comprehensive understanding of meniscal structure and function, as well as current treatments and their limitations. We aim to offer new insights to support the development of meniscus products in tissue engineering, thereby helping to lay a theoretical foundation for more accessible therapeutic solutions. Furthermore, we summarize recent advances in meniscus product research from both material and manufacturing perspectives within our laboratory. The translational potential of this article This review begins with an analysis of the macroscopic and microscopic structural characteristics of the meniscus, elucidating its critical physiological functions, thereby laying a theoretical foundation for the development of innovative meniscal repair strategy and providing structural design guidance for the construction of biomimetic meniscus. Subsequently, this review comprehensively summarizes the pathological characteristics of degenerative and traumatic tears, systematically evaluating the advantages and disadvantages of existing therapeutic approaches. Based on current clinical realities, it identifies treatment bottlenecks and unmet needs, offering reference points for research designs aligned with clinical requirements; addressing these problems specifically facilitates the translation of scientific findings into clinical products. Further, the review outlines the properties and manufacturing technologies of biomaterials, systematically comparing their performance in meeting the mechanical strength and functional demands of human meniscus, thus providing empirical references for material selection and fabrication techniques in next-generation product development. Finally, the review discusses the prospects and challenges of tissue engineering in meniscal therapy, aiming to enhance meniscal repair outcomes and provide personalized treatment protocols for patients with varying types of injuries.

Mechanical memory, or when cells retain traits from their physical environment, influences stem cell fate. During cartilage repair, the extra-cellular mechanical microenvironment could direct stem cell behavior through mechanical memory. In this study, we developed a micropattern-based method to impart mechanical memory in human synovial-derived stem cells (hSSCs), through the process of mechanical dosing. Photolithography was employed to create gelatin hydrogels with grooved patterns at the micron scale (20-200 μm). Mechanical dosing was applied by culturing hSSCs on groove-patterned hydrogel substrates for 3 days to establish mechanical memory. Based on protein and gene expression analyses, 50 μm was identified as the optimal groove size for promoting chondrogenesis. Extending the mechanical dosing period to 6 days further enhanced the effect. RNA sequencing revealed that 6 days of mechanical dosing increased expression of TGF-β3, Sox9, and ACAN genes. In a mouse model of full-thickness cartilage defect, 6 day mechanically dosed hSSCs demonstrated enhanced cartilage repair. Super-resolution imaging and microindentation assays showed that mechanical dosing reconfigures load-bearing cytoskeletal structures, establishing mechanical memory that promotes chondrogenesis via TGF-β pathway activation. Together, this study demonstrates that microgroove-patterned hydrogels could induce chondrogenic mechanical memory in hSSCs, improving their cartilage repair potential. This approach offers a promising strategy for advancing tissue engineering and regenerative medicine.

Postoperative tumor recurrence remains a fundamental limitation of curative cancer surgery, driven by residual malignant cells and a profoundly immunosuppressive postoperative microenvironment. Here, we report a tumor microenvironment-responsive hydrogel that couples self-amplifying pyroptosis with CD8+ T cells modulation to prevent postoperative tumor relapse. This hydrogel consists of a butyrate prodrug hydrogel and engineered bacterial membrane vesicles encoding a self-triggered gasdermin D-mediated pyroptosis program. Upon in situ gelation within the surgical cavity, the hydrogel undergoes controlled degradation to release the engineered pyroptosis-inducing vesicles and butyrate. The released membrane vesicles elevate intracellular gasdermin D levels while simultaneously activating the NLRP3-caspase-1 pathway, thereby triggering robust and self-amplifying pyroptosis in residual tumor cells. This lytic cell death eliminates residual malignancies and releases damage-associated molecular patterns that convert the postoperative niche from immunosuppressive to immunogenic and promote cytotoxic T lymphocytes recruitment. Concurrently, butyrate released from the hydrogel reprograms infiltrating CD8+ T cells, enhancing their effector function. By integrating tumor cell-intrinsic pyroptosis induction with modulation of antitumor CD8+ T cells, this combinatorial platform remodels the postoperative tumor microenvironment and provides durable protection against tumor regrowth. This work establishes a localized immunomodulatory strategy that directly addresses the long-standing challenge of postoperative tumor recurrence.

Conventional discectomy surgery for treating intervertebral disc (IVD) herniation remains limited in addressing post-surgery annulus fibrosus (AF) injury, resulting in high reoccurrence rate. However, repair of AF defects following discectomy remains challenging due to the complex biomechanics and anatomy of the IVD, as well as the mechanical limitations of biomaterials, which often fails to provide sufficient mechanical integration, durable tissue adhesion, and long-term biocompatibility. To address these unmet clinical challenges, we developed an adhesive hydrogel scaffold (AHS) composed of a chitosan-based fibrous hydrogels mechanical patch (FHCS, as structural support) and an alginate-catechol adhesive interface (OAD-P, as interfacial adhesive) for sealing the defect AF and preventing IVD re-herniation. FHCS exhibited strong mechanical properties (fracture strength: 46.54 ± 3.68 MPa, Young's modulus: 9.68 ± 4.17 MPa), which matched the mechanical properties of natural AF. OAD-P held strong adhesion to FHCS (shear strength: 90.1 ± 14.9 kPa) and to AF tissues (shear strength: 81.6 ± 39.9 kPa). The AHS effectively sealed the AF defect in the box defect model on rat caudal IVD, maintained the structural integrity of the defective IVD, and reduced nociceptive behavior and downregulated nociception markers, indicating its efficiency in alleviating low back pain. In the in vivo porcine lumbar spine model, the scaffold demonstrated seamless integration with AF tissue and prevented nucleus pulposus extrusion under mechanical loading. Our findings reveal the therapeutic effect and translational potential of the adhesive hydrogel scaffold for functional annular repair following discectomy.

Cancer remains a global challenge demanding innovative therapeutic strategies, particularly for metastatic cases. While iron oxide nanoparticles have gained clinical approval as iron supplements or imaging contrast agents, their standalone potential for cancer therapy remains largely unexplored. Here, we report that both photo-and ultrasound-induced mild hyperthermia (similar to 43 degrees C) can enhance iron oxide toxicity through amplified Fenton reactions and sensitize tumor cells to ferroptosis. To enhance translational potential, we refine this platform with a clinically approved iron agent of ferumoxytol and ultrasound, termed ferrultrasonic therapy (FUT). FUT can induce immunogenic cell death across multiple xenograft models and can trigger robust anticancer immune responses. Notably, FUT can significantly prolong the survival time of mice with peritoneal metastasis and achieved a 37.5% complete cure rate by 8 weeks. Overall, our work presents a translatable anticancer strategy validated in patient-derived xenograft humanized mouse models, bridging the gap in re-purposing clinically approved iron agents for oncology applications.

Osteochondral defects involve concurrent damage to cartilage and the subchondral bone. Here, a cell-free scaffold is presented, consisting of a 3D-printed bioceramic base combined with a Gelatin methacryloyl (GelMA)-Kartogenin (KGN) hydrogel. This dual induction scaffold is engineered to promote osteogenesis while simultaneously providing localized chondrogenic stimulation. The rabbit bone marrow-derived mesenchymal stromal cells are added as a positive control, while the blank osteochondral defects without scaffold implantation are set as a negative control. It is hypothesized that effective regeneration of subchondral bone is a prerequisite for functional cartilage repair, with effective recruitment of endogenous skeletal stem cells (SSCs). In rabbit osteochondral defects, chondrogenic scaffolds alone regenerated cartilage but caused severe subchondral bone collapse and joint surface deformation persisting through 24 weeks. In contrast, combining osteogenic scaffolds with chondrogenic constructs preserved joint morphology by promoting Gli-1⁺ and Sca-1⁺ skeletal stem cell recruitment and proliferation. Interestingly, adding exogenous mesenchymal stromal cells offered no further benefit. Together, a scaffold capable of recruiting endogenous skeletal stem cells to regenerate subchondral bone is essential for effective osteochondral repair and demonstrates comparable efficacy to stem cell transplantation, demonstrating the viability of a scaffold-only strategy for articular cartilage and subchondral bone tissue regeneration.

Immunologically "cold" tumors, characterized by low immune cells infiltration, represent a significant obstacle to the success of immune checkpoint therapy. Intestinal microbiome therapy has emerged as a potential strategy to overcome this challenge by reprogramming the immune microenvironment. However, its clinical application is constrained by unresolved safety concerns. To address these challenges, we fused Escherichia coli-secreted outer membrane vesicle (OMV) with the macrophage membrane vector (RV) to construct hybrid nanovesicle (ROMV) and encapsulated the bacterial metabolite trimethylamine N-oxide (TMAO), forming ROMV/TMAO. ROMV/TMAO mimicked the beneficial functions of intestinal probiotics by leveraging the immunomodulatory properties of OMV and TMAO, combined with the tumor-homing capabilities of RV. In human lung cancer organoids and multiple tumor models, selective tumor targeting and accumulation of ROMV/TMAO facilitated M1 polarization of tumor-associated macrophages and enhanced CD8+ T lymphocyte infiltration, ultimately inhibiting tumor growth. When combined with ROMV/TMAO, the immune checkpoint inhibitor α-PD-L1 exhibited superior antitumor efficacy than monotherapy. This study introduces a probiotic-inspired nanotherapeutic strategy for augmenting immune checkpoint therapy outcomes while addressing microbiome therapy safety challenges.