The efficacy of dendritic cell (DC) vaccines in cancer immunotherapy is often limited by weak immunogenicity due to inefficient antigen cross-presentation (XPT). We previously combined a calcium carbonate (CaCO3) delivery system with a proteolysis-targeting chimera (PROTAC) to enhance antigen degradation. Along this line, we developed a protein/DNA-integrated nanoantigen platform (HpOAC) co-loading CaCO3 with a His-tagged ovalbumin (O) modified with the von Hippel-Lindau (VHL) E3 ligase-recruiting peptide ALAPYIP (HOA) and a eukaryotic plasmid encoding O-ALAPYIP (pOA). HpOAC promoted DC maturation and migration via Ca2+ release. Mechanistically, HOA provided an immediate antigen source, while pOA enabled sustained expression; both underwent ALAPYIP-mediated VHL recruitment, enhancing O ubiquitination and proteasomal degradation, thereby amplifying XPT. Consequently, HpOAC-DCs induced strong OT-I/OT-II T cell proliferation in vitro. In vivo, a single immunization with HpOAC-DCs significantly suppressed tumor growth and elicited durable antigen-specific T helper type 1 and cytotoxic T lymphocyte responses, outperforming single-antigen vaccines. Under a two-dose regimen, its anti-tumor efficacy was improved compared to non-PROTAC and in situ antigen vaccines. Thus, we constructed a PROTAC-enhanced, protein/DNA-integrated DC vaccine platform that synergizes immediate and sustained antigen supply with Ca2+-mediated adjuvanticity, offering a highly promising strategy for novel DC vaccine design.

Dendritic cells (DCs) can activate T cells to trigger sustained antitumor immune responses, a process in which the continuous migration of antigen-loaded DCs from the tumor microenvironment to tumor-draining lymph nodes is critical. DCs have evolved a complex and dynamic regulatory network to mediate their migration to specific locations, with multiple transporters including amino acid transporters reported to participate in this process. Slc1a2 is highly expressed in the nervous system, where it mediates the clearance of extracellular glutamate, primarily in astrocytes; however, its role in the immune system remains unclear. In this study, we showed that activated DCs upregulated Slc1a2 to boost glutamate uptake, which in turn promoted DC functionality and antitumor vaccine potency. Furthermore, glutamate signaling induced Sema3A, which elevated small GTPase signaling pathways (e.g., RhoA/Rac1/Cdc42) and drove dynamic cytoskeletal remodeling, thereby providing the necessary molecular machinery for DC migration during antitumor immunity in vivo. We first demonstrated that Slc1a2-mediated glutamate metabolism functioned as a metabolic checkpoint for DC migration and antigen-specific immunity in vivo, with the Sema3A/small GTPase axis serving as the core mechanism linking glutamate signaling to cytoskeletal reorganization.

Background Two immunological events usually occur in anti-tumor immunity. On the one hand, tumor cells present endogenous tumor antigen to activate CD8+ cytotoxic T lymphocytes (CTLs) via direct presentation. On the other hand, professional antigen presenting cells (APCs), such as dendritic cells (DCs), take up exogenous tumor antigen for the CTL activation through cross-presentation (XPT). However, in actual tumor settings in vivo, tumor cells not only reduce their own antigen direct presentation by down-regulating major histocompatibility complex (MHC) I molecules, but also impair the XPT from DCs by producing immunosuppressive factors such as prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-10, and so on, leading to the failure of immunosurveillance and subsequent tumor growth.Methods We first summarize the latest studies on different mechanisms of XPT, before different types of DC vaccines and recent advances in XPT-based cancer immunotherapeutic strategies are described.Results Emerging studies have elucidated multiple pathways and molecular regulators of XPT in DCs. Different types of DC vaccines have been developed to optimize XPT and improve CTL activation. Furthermore, innovative strategies targeting immunosuppressive factors in the tumor microenvironment (TME) have shown promise in enhancing the efficacy of XPT-based immunotherapies.Conclusion Deep insight of XPT in DCs and its affecting factors in tumor immunology will hopefully lead to better therapeutic translation in clinical treatment of tumor, the fatal disease that has threatened human life for centuries.

A thrombophilic tendency (thrombophilia) is a hypercoagulable state that significantly increases the risk of thromboembolic events. Although conventional anticoagulant therapy is effective, the inherent risk of bleeding limits its long-term use, creating an urgent need for safer and more effective alternatives. Nattokinase (NK)- a serine protease derived from the fermentation of natto by Bacillus subtilis- exerts its antithrombotic effects through multiple mechanisms and targets, including direct degradation of fibrin, inhibition of platelet aggregation, and antioxidant/anti-inflammatory actions, while offering oral bioavailability and potential for long-term prevention. However, bottlenecks such as insufficient pH and thermal stability, limited clinical evidence, and a lack of standardization hinder its translation into clinical practice.This review systematically integrates the multifunctional mechanisms and pharmacokinetic characteristics of NK, proposing a ‘dynamic equilibrium model of thrombolysis and haemostasis’ as a theoretical framework to guide end-to-end optimization from molecular modification to personalized therapy. We first compare and evaluate the therapeutic advantages of NK against traditional and novel antithrombotic drugs. And then we critically analyze the technical maturity and clinical feasibility of engineering modifications (surface charge regulation, regional stiffening, AI-assisted design) and delivery systems (polysaccharide encapsulation, liposomes, nanocarriers). Finally, we identify priority research areas such as standardized production, genotype-guided dosing and trials in high-risk populations, thereby providing a roadmap for the translation of NK from functional foods to clinical drugs.

Background/Objectives: In situ vaccines that directly release endogenous tumor antigens in situ to elicit anti-tumor immune responses without exogenous antigen preparation have emerged as a promising cancer immunotherapy strategy, due to their enhanced safety by local immunization that minimizes systematically adverse reactions. However, the anti-tumor efficacy of most in situ vaccines is affected by their limited access to tumors in distant sites and the toxicity of the adjuvants contained. Methods: To overcome these shortcomings, the present study explored the feasibility of utilizing extracellular vesicles from the probiotic bacteria Lactococcus lactis as both immune activators and drug carriers, which were formulated into nanoparticles to target distant tumors. Results: Using confocal microscopy and flow cytometry, we confirmed that the Lactococcus lactis-derived extracellular vesicles possess adjuvant activity that promoted the maturation of dendritic cells without affecting their viability or apoptosis rate. Moreover, the Lactococcus lactis-derived extracellular vesicles, both alone and when carrying the drug doxorubicin, could target and accumulate in solid tumor tissues via the enhanced permeability and retention effect. Interestingly, compared to healthy cells, the Lactococcus lactis-derived extracellular vesicles tended to be taken up more by tumor cells and readily released their encapsulated doxorubicin in the acidic tumor environment, which resulted in their enhanced reactive oxygen species production and immunogenic cell death. Ultimately, systemic administration of Lactococcus lactis-derived extracellular vesicle-encapsulated doxorubicin greatly increased the anti-tumor efficacy by boosting the number of infiltrating dendritic cells and CD8+ T cells in the tumor tissues and doxorubicin-mediated immunogenic cell death. Conclusions: Collectively, this study demonstrated that the probiotic Lactococcus lactis-derived extracellular vesicles are both safer adjuvants and effective drug carriers with immunostimulatory activity and tumor-targeting capability, shedding an interesting light on this vaccine design platform for future cancer immunotherapy.

Mannan oligosaccharides (MOS) are valuable prebiotics, and enzymatic hydrolysis by β-mannanase is the preferred production route. Bacillus-derived GH26 β-mannanase (gmuG) holds industrial promise but suffers from low catalytic efficiency and weak pH stability. Here, we rationally engineered flexible loops near the active site via molecular dynamics, NMsim (normal mode-based geometric simulation), sequence conservation analysis, and MAESTRO prediction, and obtained the optimal double mutant M1 (E301K-T271V). Relative to the wild type, M1 showed 1.54-fold higher specific activity and nearly 2-fold improved pH stability at pH 8, with a nearly doubled kcat while retaining substrate affinity. Mechanistically, M1 enlarged the active site, shortened the attack distance of the catalytic residue, increased α-helix content, and rigidified neighboring loops. Fermentation optimization in Escherichia coli gave a maximum yield of 924.34 U/mL. This work offers an effective strategy for β-mannanase engineering and a high-performance biocatalyst for industrial MOS production.

For almost a century, our understanding of cancer metabolism has been dominated by the Warburg effect, the view that cancer cells suppress mitochondrial respiration and depend on aerobic glycolysis. This binary view can no longer explain the metabolic heterogeneity observed in malignancies. Mitochondrial oxidative phosphorylation, abbreviated OXPHOS, is not broadly silenced in cancer: compelling evidence shows that it is preserved or even upregulated in drug-resistant tumors, cancer stem cells, and tumors growing in metabolically constrained microenvironments, yet it has been pursued as a therapeutic target for years with little clinical success. This review critically reevaluates the Warburg-centric model and integrates new mechanistic insight into cancer-associated OXPHOS, covering somatic mitochondrial DNA mutations found in more than half of human cancers, retrograde redox signaling driven by mitochondrial reactive oxygen species, oncogene-directed metabolic reprogramming, and remodeling of the mitochondrial network. A central theme is metabolic plasticity, the capacity to switch dynamically between glycolysis and OXPHOS rather than addiction to a single pathway. We discuss why this plasticity, together with the on-target toxicity of electron transport chain inhibitors in normal tissues, has led to the termination of all major clinical trials of direct OXPHOS inhibitors. Microenvironmental metabolic symbiosis and intercellular mitochondrial transfer add further complexity that defeats single-agent strategies. Future progress will require tumor-specific metabolic and redox phenotyping for patient stratification, rational combination therapies, and therapeutic concepts beyond direct electron transport chain inhibition. Recognizing metabolic complexity past the Warburg-OXPHOS dichotomy is essential for precision cancer medicine.

Previous studies on Ficus carica polysaccharides (FCPS) showed promising antidiabetic activity but were limited by poor stability and low bioavailability. To overcome these limitations and enhance both the hypoglycemic efficacy and stability of FCPS, this study utilized a green synthesis method to modify FCPS with gold nanoparticles, resulting in FCPS-gold nanoparticles (FCPS-AuNPs). FCPS-AuNPs were synthesized using a chloroauric acid reduction method with FCPS. The morphological structure and physicochemical characteristics of FCPS-AuNPs were characterized various techniques, revealing that spherical AuNPs formed gold-sulfur bonds with FCPS. In vitro, FCPS-AuNPs exhibited stability and hypoglycemic activity, and were non-toxic to HepG2 cells at concentrations up to 200 μg/mL. In vivo, FCPS-AuNPs significantly reduced liver, kidney, and pancreatic damage, inhibited adipose tissue morphology changes in diabetic mice, and improved glucose and lipid metabolism by ameliorating insulin resistance, regulating immune response, and decreasing pro-inflammatory factors TNF-α and INF-γ. The hypoglycemic activity of FCPS-AuNPs was markedly superior to that of FCPS alone, possibly by modulating the IRS-1/PI3K/AKT/GSK3β pathway. These findings collectively indicate that FCPS-AuNPs have significant potential as a strong antidiabetic agent for food and pharmaceutical applications.

Targeted protein degradation (TPD) has transformed the landscape of drug discovery by exploiting the ubiquitin-proteasome system (UPS) to eliminate, rather than inhibit, pathogenic proteins. This paradigm shift enables access to a vast array of previously “undruggable” targets and offers new therapeutic opportunities across diverse diseases. Among the available approaches, proteolysis-targeting chimera (PROTAC) have rapidly advanced from concept to clinical evaluation. Here we highlight the unique advantages of PROTAC in disease treatment and target identification, and examine emerging solutions to address key challenges such as pharmacokinetics, E3 ligase diversity, and selectivity. Together, these advances define a new era of precision therapeutics based on the controlled elimination of disease drivers.

Metabolic reprogramming, especially the upretoning and functional reshaping of glycolysis, is the cornerstone of cancer progression, driving proliferation, invasion and metastasis. This review systematically analyzes the Warburg effect. This metabolic transformation promotes the progression of malignant tumors by enhancing glucose uptake, lactate production and microenvironmental remodeling. We elaborated on the molecular basis of this process, focusing on the oncogenic dysregulation of key glycolytic enzymes such as hexokinase 2 (HK2), phosphofructose kinase-1, pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). These malfunctions are usually driven by hyperactive signaling pathways such as PI3K/AKT/mTOR and HIF-1α. This metabolic remodeling also actively shapes the tumor microenvironment (TME) by promoting acidosis, inhibiting anti-tumor immunity and stimulating angiogenesis. Intermediate metabolites in the process of glycolysis can also be used as signal nodes to regulate epithelial-mesenchymal transition (EMT) and maintain the plurity of cancer stem cells (CSC). The cyclic flux of the pentose phosphate pathway (PPP) and the truncated tricarboxylic acid (TCA) cycle flux further highlight the metabolic flexibility inherent in malignant cells. Finally, we critically evaluated emerging treatment strategies for these glycolysis vulnerabilities, including inhibitors of HK2, glucose-6-phosphate dehydrogenase (G6PD), fructose-2,6-diphosphatase3 (PFKFB3) and LDHA. This review reinforces the central position of glycolysis metabolism and emphasizes the potential of tumor treatment.

With cancer increasingly managed as a chronic disease, there is a critical need for technologies that enable sensitive, multiplexed, and dynamic profiling of immune molecules across the cancer continuum. Surface-enhanced Raman scattering (SERS), with its advantages of high throughput, ultra-high sensitivity, multiplexed biomarker detection, and dynamic tracking, has emerged as a key platform for molecular phenotyping and continuous disease monitoring. This review elucidates how recent knowledge in nanostructured SERS probes have facilitated the transition from static molecular detection to dynamic molecular analysis, with advances in hotspot engineering, targeted and label-free frameworks, and spatiotemporal imaging methods. Particular emphasis is placed on the analysis of representative tumor-/immune-related molecular biomarkers, to align with clinical needs spanning from acute disease management to long-term chronic care. We also discuss ongoing challenges and prospects in SERS standardization, scalable fabrication, and AI-assisted clinical translation.

Although nanozymes are potential tumor therapeutics due to their ability to disrupt intracellular redox homeostasis, developing nanozymes with higher therapeutic efficacy and clarifying their antitumor mechanism are challenging. Here, an iridium (Ir)-based nanozyme (IIN) was constructed through coordination-driven co-assembly using photosensitizer indocyanine green (ICG), Ir, and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG8189. Then, the IIN was mimicked by tumor cell lysate (TCL)-simulated dendritic cell (DC) membrane to form IIN@M. Based on superior enzyme-like activity and photothermal performance, IIN@M disrupted the intracellular redox homeostasis by generating reactive oxygen species (ROS) and depleting glutathione (GSH). GSH depletion induced ferroptosis, and ROS burst under photothermal irradiation triggered pyroptosis, thus synergistically enhancing immunogenic cell death (ICD). The generated ROS could promote mitochondrial DNA (mtDNA) oxidative damage and release, finally activating the immune response by the cyclic GMP-AMP synthase-simulator of interferon gene (cGAS-STING) pathway. In vivo experiments also suggested that IIN@M could efficiently ablate the primary tumor, especially under photothermal irradiation. Furthermore, it could suppress distant tumor progression by triggering the immune response, especially under photothermal irradiation, which was accompanied by increased DC maturation, M1 macrophage polarization, and T cell infiltration in tumor tissue. This study proposed a promising strategy for effective Ir-based nanozyme in tumor immunotherapy.

Multidrug resistance (MDR) is a central cause of chemotherapy failure and tumor recurrence and metastasis, and its mechanism involves enhanced drug efflux, target mutation, upregulation of DNA repair and remodeling of the tumor microenvironment. ABC transporter protein (P-gp, MRP, and BCRP)-mediated efflux of drugs is the most intensively researched aspect of the study, but the first three generations of small-molecule reversal agents were stopped in the clinic because of toxicity or pharmacokinetic defects. Natural products are considered as the fourth generation of MDR reversal agents due to their structural diversity, multi-targeting and low toxicity. In this paper, we systematically summarize the inhibitory activities of monoterpenes, sesquiterpenes, diterpenes and triterpenes against ABC transporter proteins in in vitro and in vivo models and focus on the new mechanism of reversing drug resistance by blocking efflux pumps, modulating signaling pathways such as PI3K-AKT, Nrf2, NF-κB and remodeling the tumor microenvironment. For example, Terpenoids possess irreplaceable core advantages over traditional multidrug resistance (MDR) reversers: Compared with the first three generations of synthetic reversers, natural/semisynthetic terpenoids integrate low toxicity (mostly derived from edible medicinal plants, half-maximal inhibitory concentration IC50 > 50 μM), high target specificity (e.g., oleanolic acid specifically inhibits the ATP-binding cassette (ABC) transporter subtype ABCC1 without cross-reactivity with ABCB1), and multi-mechanistic synergistic effects (e.g., β-caryophyllene simultaneously mediates the dual effects of “ABCB1 efflux inhibition + apoptotic pathway activation”). These unique characteristics enable terpenoids to effectively circumvent key limitations of traditional synthetic reversers, such as high toxicity and severe drug–drug interactions. Among them, lupane-type derivative BBA and euphane-type sooneuphanone D (triterpenoids), as well as dihydro-β-agarofuran-type compounds and sesquiterpene lactone Conferone (sesquiterpenoids), have emerged as the core lead compounds with the greatest translational potential in current MDR reverser research, attributed to their potent in vitro and in vivo MDR reversal activity, low toxicity, and excellent druggable modifiability. At the same time, we point out bottlenecks, such as low bioavailability, insufficient in vivo evidence, and unclear structure–activity relationship and put forward a proposal to address these bottlenecks. At the same time, the bottlenecks of low bioavailability, insufficient vivo evidence and unclear structure–activity relationship have been pointed out, and future research directions such as nano-delivery, structural optimization and combination strategies have been proposed to provide theoretical foundations and potential practical pathways for the clinical translation research of terpenoid compounds, whose clinical application still requires further in vivo validation and translational research support.

Tomato pomace is an abundant food-processing by-product whose terpenoid fraction remains underexplored. This study established an integrated workflow combining extraction optimization, resin enrichment, activity-guided fractionation, LC–MS profiling, and candidate prioritization to explore bioactive terpenoid-rich fractions from tomato pomace. Ultrasound–microwave-assisted extraction was optimized using response surface methodology, yielding 23.99 ± 0.07 mg/g total terpenoids under the validated conditions. Subsequent enrichment with D101 macroporous resin increased the total terpenoid content to 46.61 ± 1.12 mg/g. LC–MS profiling of the most active fraction tentatively annotated 334 terpenoid-related compounds. Based on relative abundance, previously reported biological activity, and commercial availability, six candidates were selected for comparative evaluation. Among the compounds tested, isoalantolactone (IAL) exhibited the strongest concentration-dependent antiproliferative activity against prostate cancer cells and was therefore prioritized for further investigation. Computational analyses highlighted GSK3β-associated signaling as a potential pathway-level candidate. Cellular assays further associated IAL treatment with ROS accumulation, mitochondrial dysfunction, apoptosis, reduced glycolytic activity, and changes in GSK3β/β-catenin-associated protein expression. In an RM-1 tumor-bearing mouse model, IAL reduced tumor growth, with no treatment-associated abnormalities detected in the monitored body-weight, organ-index, histological, or serum biochemical endpoints. Overall, this study provides an integrated recovery-to-prioritization strategy for screening bioactive candidates from tomato pomace and identifies IAL as a prioritized compound for further source confirmation and food-relevant evaluation.

Chickpea (Cicer arietinum L.) is a major annual legume crop with a balanced nutritional profile and a broad spectrum of bioactive constituents; these characteristics have made it a useful ingredient in health-oriented food applications. Chickpea supplies protein that is readily absorbed and digested, along with isoflavones and other bioactive plant compounds that act on physiological pathways associated with chronic disease prevention. Nonetheless, the combined pressures of drought, heat, cold, and salinity persistently limit its yield potential and cultivation stability. This review integrates the most recent progress in chickpea research, with emphasis on its intrinsic value derived from macronutrients, micronutrients, and bioactive metabolites. It further synthesizes the physiological determinants and metabolic reprogramming mechanisms underlying abiotic stress tolerance, outlines precision breeding strategies for developing resilient and high-quality ideotypes, and examines pathways for the high-value utilization of chickpea-derived processing by-products. Future efforts should focus on developing stress-resilient cultivars and expanding chickpea’s application in functional food innovation.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral issues, posing significant public health challenges. Small interfering RNAs (siRNAs) offer the potential to selectively silence AD-related pathogenic genes. This review first outlines the diverse pathogenic mechanisms and hallmark pathologies of AD, then spotlights the key genes now being silenced by siRNA for therapeutic intervention. These genes encompass those directly implicated in amyloidogenesis, tau phosphorylation, and neuroinflammation, along with those aberrantly up-regulated and associated with AD pathology. Finally, it summarizes recent research on non-viral and local siRNA delivery strategies including lipid, polymer, quantum dots, inorganic materials, extracellular vesicles, and conjugates aimed at effectively penetrating the blood-brain barrier while overcoming intra- and extracellular barriers to target key AD pathways. These findings underscore the promise of siRNA therapy in addressing AD pathology and provide valuable insights into overcoming delivery challenges.

Glycyrrhiza uralensis polysaccharides (GUPS) are considered safe and effective natural medicine due to their extensive pharmacological activity and low toxicity. However, their large molecular weight (approximately 29 kDa) and high polarity restrict intestinal absorption, resulting in poor oral bioavailability. Here, GUPS-PLGA nanoparticles (GUPS-PLGA NPs, GPN) were prepared and their intestinal absorption characteristics and immunostimulatory activity were evaluated both in vitro and in vivo. Notably, GPN with a high encapsulation rate (63.18%) was prepared by response surface methodology. Furthermore, GPN exhibited a uniform spherical shape with a 242.4 ± 3.18 nm particle size, good stability, and sustained-release properties. Oral administration of GPN enhanced the intestinal retention of GUPS and improved its transport capacity in a Caco-2 cell monolayer model (0.66 vs. 1.36 Papp×10-6 cm/s). More importantly, GPN markedly promoted dendritic cell (DC) maturation through direct interactions and indirect effects across the Caco-2 cell monolayer. Furthermore, GPN significantly increased the number and activation state of T cells, DC, and macrophages in mice's spleen and mesenteric lymph nodes (MLN), demonstrating superior immune-enhancing effects. In summary, the PLGA-based oral drug delivery system markedly improved GUPS's intestinal absorption and efficacy, providing a theoretical foundation for developing GUPS as an oral medication and functional food.

The biological activities of polysaccharides are affected by a variety of factors such as monosaccharide composition, molecular weight, glycosidic bond type, branching degree, molecular conformation and functional groups, and are closely related to structural features. In order to clarify the structure of polysaccharides as much as possible, it is necessary to characterize and simulate the structure of polysaccharides based on primary structure characterization, and further describe or visualize the three-dimensional structure of polysaccharides. A large number of studies have shown that polysaccharides from different sources and structures participate in or directly exert their activities in the fields of anti-tumor, anti-oxidation, and immune regulation related to immunology, anticoagulation, hypoglycemia, lipid-lowering, anti-fatigue, and other activities. The structural modification/modification of polysaccharides provides the possibility to improve the activity, efficiency, or functional specificity of polysaccharides. Due to the diversity and complexity of the structure of polysaccharides, the structural prediction is not complete and of high accuracy, and the functional prediction is limited by the diversity of binding receptors, so the downstream pathways involved cannot be accurately located. Therefore, it is necessary to consider the comprehensive results from multiple perspectives in the study of the mechanism of exerting biological activity. Structural detection and analysis of polysaccharides are inextricably linked to the development of polysaccharide biological activities, which can be easily predicted through structural analysis and summarization of structural patterns.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 80% of cases. Conventional chemotherapy is severely limited by insufficient tumor targeting, severe off-target systemic toxicity, and poor bioavailability of hydrophobic antitumor agents, which greatly compromise therapeutic efficacy and patient quality of life. Phytosphingosine (PHS), a natural sphingolipid with potent antitumor activity via cell cycle regulation and apoptosis induction, is hindered by low water solubility and dose-dependent systemic toxicity, restricting its clinical translation. To address these critical obstacles, we fabricated a biomimetic liposomal nanosystem (PHS-LPs@CCM) by camouflaging PHS-loaded liposomes with homologous NCI-H1299 lung cancer cell membranes. The resulting nanoparticles exhibited favorable colloidal stability, uniform size distribution, and excellent hemocompatibility, with the membrane coating retaining native surface adhesion molecules for specific homotypic recognition. This bioinspired design markedly enhanced cellular internalization in NCI-H1299 cells compared with uncoated liposomes. In vitro functional studies demonstrated that PHS-LPs@CCM induced significant G0/G1 phase arrest and ROS-dependent mitochondrial apoptosis, while effectively suppressing cell migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) process. This biomimetic colloidal platform offers a promising strategy to improve the delivery, efficacy, and safety of hydrophobic antitumor drugs, providing valuable implications for the design of biointerfacial functional nanocarriers for targeted cancer therapy.

Ovarian cancer, a highly lethal gynecological malignancy with high recurrence rates and low survival, poses significant treatment challenges. While immunotherapy, particularly dendritic cell (DC) vaccines, boosts immune responses, its clinical efficacy is limited by poor antigen presentation and weak lymph node targeting. To address this, we develop a novel biomimetic nanovaccine (GA-NPs@DCV) using cell membrane-coated nanoparticles that incorporate the natural anti-tumor agent galangin (GA) and ovarian tumor-associated antigens (TAAs). GA-NPs@DCV features the antigen-presenting functions of DCs and utilizes GA to induce tumor immunogenic cell death (ICD), which not only endows the vaccine with abundantly processed specific TAAs, but also ensures robust homing capability to lymph nodes and the tumor microenvironment. Interestingly, in OT-I/OT-II transgenic mice, GA-NPs@DCV enhances the proliferation of CD8+ and CD8+ IFN-γ+ cells to activate potent immune responses. Furthermore, a nano-DC vaccine carrying distinct antigens (NPs@DCV) not only inhibits tumor growth and activates systemic immune responses, but also effectively prevents tumor recurrence. Importantly, GA-NPs@DCV exerts potent anti-ovarian cancer effects by promoting immune activation, inhibiting immune evasion through the Stat3/IDO1/AhR signaling axis, and remodeling tumor immune microenvironment via regulation of the tryptophan metabolic pathway. Notably, GA-NPs@DCV also promotes the generation of tissue-resident memory T cells (TRM, CD8+CD103+ cells) within tumor tissue, effectively inducing long-term protective immunity. Overall, these findings identify GA-NPs@DCV as an effective personalized nanovaccine that can simultaneously deliver tumor antigens and the Stat3 inhibitor GA to the tumor microenvironment to exert potent antitumor effects, providing a promising immunotherapeutic strategy for ovarian cancer.