Despite the rising global incidence of inflammatory bowel disease (IBD), curative therapies remain unavailable. While our previous work implicated the intestinal proteoglycan Syndecan-1 (SDC1) in IBD-associated barrier dysfunction and inflammation, the underlying mechanism was unclear. This study aimed to elucidate how SDC1 maintains intestinal barrier integrity through interactions with the gut microbiome. In DSS-induced colitis, global knockout of Sdc1 (Sdc1-/-) exhibited exacerbated inflammatory infiltration and greater impairment of barrier structure and function than wild-type (WT). Formation of intestinal organoids was independent of genotype, indicating that Sdc1-/- does not impair barrier function via disrupting epithelial development. The heightened colitis susceptibility in Sdc1-/- mice was abolished in the antibiotic-treated pseudo-germ-free models, and transmissible to WT mice via fecal microbiota transplantation. Similar results were reproduced in a germ-free mouse model. Metagenomic sequencing identified Faecalibacterium prausnitzii as the most significantly depleted species upon Sdc1 knockout. In vitro, SDC1-attached glycosaminoglycans (heparan sulfate (HS) and chondroitin sulfate (CS)) but not the SDC1 core protein promoted F. prausnitzii growth. Prokaryotic transcriptome profiling indicated that HS/CS induces cobalamin biosynthesis in F. prausnitzii. The critical role of cobalamin as a mediator was confirmed, as its synthetic inhibition significantly diminished the growth-promoting effect of HS/CS. Mechanism studies showed that HS/CS enhanced biofilm formation in F. prausnitzii, thereby facilitating cobalamin biosynthesis. Oral administration of HS ameliorated DSS-induced colitis and promoted mucosal colonization of F. prausnitzii, independent of the host genotype. Finally, human IBD biopsies revealed a positive correlation between epithelial SDC1 and mucosal F. prausnitzii, as well as an inverse correlation with bacterial translocation and the number of LPS‑positive cells. Our study elucidates a novel mechanism in which the glycosaminoglycan chains of SDC1 promote F. prausnitzii colonization and growth through enhanced biofilm formation and cobalamin synthesis, thereby highlighting the therapeutic potential of HS for IBD and offering a new basis for host-directed microbiota regulation.

In recent years, the application of microfluidic chips in atherosclerosis (AS) research has garnered significant attention. This technology, renowned for its precise control of fluid dynamics at the microscale and its ability to stimulate complex physiological environments, has emerged as a powerful tool for studying AS pathogenesis and conducting drug screening. This study reviews the essential materials for microfluidic chips and their functional characteristics, exploring the application scenarios of various materials in terms of biocompatibility, physicochemical properties, and process adaptability. It focuses on the core technologies and recent advancements in microfluidic chips for stimulating hemodynamics, cell culture, and multicellular interactions, particularly in key pathological processes of AS, such as early lesion formation, thrombosis, and inflammatory responses. Additionally, the article highlights major challenges and future directions for the clinical translation of microfluidic chips, including material innovation and advanced manufacturing techniques for complex structures. These studies provide critical support for understanding AS mechanisms and therapies, while envisioning their potential in personalized medicine.

The effectiveness of colorectal cancer (CRC) treatment remains constrained due to the limited drug delivery efficiency resulting from the intestinal epithelial barriers. Although solid nanoparticle-mediated drug delivery systems can enhance drug penetration, most of them are digested and excreted from the body, with only a small portion successfully crossing the intestinal epithelial barrier. Herein, we demonstrated lemon-derived extracellular vesicles (EVs)-engineered oral capsules loaded with capecitabine (EVOC), enabling them to trigger temporary opening of the intestinal epithelial barrier as a result of mechanical stress and thereby greatly enhancing the drug delivery efficiency. The EVOC enabled them to induce cellular stress responses within the intestinal epithelial barrier due to their much larger dimensions than cells, resulting in cytoskeleton relaxation and thereby breaking the original balance of tight junctions among cells. This cellular stress response could temporarily open the intestinal epithelial barrier, allowing highly efficient drug penetration into tumor tissues. The concentration of 5-fluorouracil (metabolite of capecitabine) accumulated in tumor tissues within the EVOC group was approximately 13-fold higher than that in the free capecitabine group and 6-fold higher than that in the capecitabine@EV nanodrugs. As expected, the EVOC group significantly enhanced the chemotherapy efficiency of CRC.

Glycogen storage disease type Ib (GSD-Ib) is commonly associated with refractory inflammatory bowel disease (GSD-IBD). Although the SGLT2 inhibitor empagliflozin has demonstrated remarkable clinical efficacy, its direct effects on the intestinal epithelium remain poorly understood. This study aimed to determine whether empagliflozin directly restores the impaired colonic mucus barrier and to identify the underlying molecular pathway. In terms of efficacy, we integrated clinical evaluations of GSD-IBD patients with a novel murine model of epithelial injury induced by a defined bacterial consortium (EVS: Enterococcus, Veillonella, Streptococcus) and dextran sulfate sodium (DSS). In vitro, we employed Caco-2 cells and intestinal organoids, combined with pharmacological inhibition of AMPK and siRNA-mediated gene knockdown to elucidate the underlying molecular mechanisms. Clinical data indicated that empagliflozin promoted ulcer healing and enhanced mucin production in patients. In the EVS + DSS mouse model, empagliflozin treatment reduced disease severity and attenuated goblet cell depletion. We demonstrated that empagliflozin upregulates the transcription factor SOX4 in intestinal epithelial cells both in vivo and in vitro, an effect dependent on AMPK activation. Notably, siRNA knockdown of SOX4 abolished empagliflozin-induced MUC2 upregulation. Furthermore, pharmacological inhibition of AMPK suppressed the induction of MUC2, which could be rescued by SOX4 overexpression. Our findings uncover a novel, epithelium-intrinsic mechanism of action for empagliflozin: the activation of the AMPK/SOX4/MUC2 signaling axis to restore the colonic mucus barrier. These results provide a mechanistic foundation for the repurposing of SGLT2 inhibitors in conditions characterized by epithelial barrier dysfunction.

In the tumor microenvironment, both tumor cells and tumor-associated macrophages (TAMs) frequently impede the effective treatment of glioblastoma (GBM). Herein, a co-extracellular vesicles (EVs) delivery system composed of M0 RAW264.7 macrophage-derived extracellular vesicles (MEVs) and doxorubicin (DOX)-loaded lemon-derived EVs (LEVDs) is demonstrated, enabling a significant enhancement of immunochemotherapy for GBM. This system facilitates the penetration of both EV types across the blood-brain barrier and blood-brain tumor barrier, enabling precise modulation of TAMs and tumor cells within the GBM microenvironment. During this process, MEVs exhibit a remarkable homing capacity toward TAMs, and meanwhile, they are enriched in microRNA let-7f-5p, which targets the 3' untranslated region of A20 mRNA in M2 macrophages, leading to the activation of nuclear factor κB signaling pathway. This cascade drives the repolarization of M2 macrophages toward an M1 phenotype, effectively reversing the immunosuppressive tumor microenvironment. Concurrently, LEVDs exhibit exceptional targeting of GBM cells through receptor-ligand interactions, facilitating efficient chemotherapy. As expected, the co-EVs delivery system significantly enhances immunochemotherapy for GBM through MEVs-mediated TAM repolarization and LEVDs-driven chemotherapy.

Current nanoparticle-based drug delivery systems present significant challenges in treating solid tumors, primarily due to a variety of physiological and pathological barriers that hinder the deep penetration of drugs. Herein, we demonstrate bio-inspired fractal-structured gel-drugs (DOX@HPLA, DHPL) that significantly enhance deep tumor penetration, thereby greatly improving the chemotherapy efficiency for hepatocellular carcinoma (HCC). The fabrication of DHPL is achieved through a crosslinking of 8-arm polyethylene glycol (PEG) and polysaccharide heparin in the presence of DOX, which is subsequently modified with targeting lactobionic acid (LA). During the process of penetration, these fractal-structured gel-drugs could leverage their soft and rough surfaces endowed by their unique fractal structures to increase the interfacial contact sites with the tumor cells through topographic interactions, which optimizes the cell adhesion in the local area. This results in a significant enhancement of interfacial adhesion and internalization, thereby substantially improving receptor-mediated endocytosis associated with subsequent transcytosis. In the process of transcytosis, the fractal-structured geldrugs facilitate the early endosomes/recycling endosomes pathway for exocytosis and concurrently diminish degradation in the early endosomes/late endosomes/lysosome pathway, resulting in deeper tumor penetration and thereby enhancing the chemotherapy efficiency for HCC. It is believed that the bio-inspired fractal-structured gel-drugs enable efficient amplification of interfacial interactions with cells through fractal-structuremediated topographic interactions, providing an avenue for deep penetration treatment of solid tumors.

Intestinal fibrosis represents a common complication of Crohn’s disease (CD). Previous studies have shown that PIEZO1 is enriched in the colonic mucosal epithelial cells of patients with CD. However, whether epithelial PIEZO1 contributes to intestinal fibrosis in CD remains unclear. The present study investigated whether PIEZO1 in intestinal epithelial cells (IECs) regulates intestinal fibrosis by modulating macrophage-to-myofibroblast transition (MMT). Western blotting, real-time PCR, Masson’s trichrome staining and immunofluorescence were used to evaluate the association between PIEZO1 and MMT in vivo and in vitro. Conditioned medium (CM) derived from IECs was used to assess its effects on macrophage phenotype. Co-immunoprecipitation, single-cell RNA sequencing and Enzyme-linked immunosorbent assay were performed to identify the mechanism through which PIEZO1 signaling in IECs regulates MMT. Intestinal fibrosis in patients with CD was positively correlated with the MMT process. CM derived from IECs with elevated PIEZO1 activity promoted MMT. Mechanistically, elevated PIEZO1 activity in IECs was associated with increased TGF-α secretion, which was accompanied by activation of the PKA/NF-κB P65 signaling pathway in macrophages. Furthermore, in a chronic DSS-induced colitis–associated fibrosis model, IEC-specific PIEZO1 deficiency attenuated intestinal fibrosis. These findings suggest that epithelial PIEZO1 regulates MMT and intestinal fibrosis in CD, potentially involving TGF-α–mediated signaling.

Seven cis-Pt(II) complexes (C1–C7) bearing a common salicylaldimine chelating ligand and structurally varied isocyanide co-ligands were synthesized to investigate how the co-ligand functionalization regulates crystal packing, emission behavior, and light-dependent antiproliferative activity. The structures of the obtained complexes were characterized by nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry and single-crystal X-ray diffraction analysis. The results confirmed their stable square-planar configuration and multidimensional crystal stacking structure. Photophysical analyses of these complexes revealed obvious AIE or solid-state phosphorescence with large Stokes shifts value. C7 showed the strongest emission in 90% water/THF mixture, whereas C3 exhibited the strongest solid-state emission. In vitro photodynamic antiproliferative assays demonstrated that the inhibitory effects of C3 and C7 against HeLa, HepG2, MKN45 and A549 cells were remarkably enhanced under white light irradiation. Notably, C7 displayed excellent photodynamic antiproliferative capacity and synergistic chemotherapeutic potential, with a low phototoxic IC₅₀ value of 0.78 μM and a high phototoxicity index (PI) of 7.58 toward HeLa cells. These findings demonstrated that the steric and structural properties of isocyanide co-ligands significantly influence molecular packing, emission, and light-enhanced antiproliferative activity.

Inflammatory bowel disease (IBD) remains a significant therapeutic challenge, with current agents plagued by suboptimal efficacy and safety issues. While gut microbiota dysbiosis is increasingly acknowledged as a key driver of IBD pathogenesis, the identification of functionally characterized, translationally applicable microbial-metabolic axes remains an unmet need. Here, we demonstrate that Clostridium sporogenes (C. sporogenes) is significantly decreased in both IBD patients and experimental colitis models. Notably, supplementation with this commensal bacterium markedly alleviates disease severity in both DSS-induced chemical colitis and Il10-/- spontaneous genetic colitis, thereby validating its therapeutic potential. Critically, we reveal that the protective effects of C. sporogenes are mediated by its secretion of the bioactive metabolite cis-aconitic acid (CAA). We further establish that aconitate hydratase A (AcnA) is essential for CAA biosynthesis: an acnA-knockout C. sporogenes strain fails to produce CAA and loses therapeutic efficacy, whereas engineered Escherichia coli overexpressing acnA recapitulates both CAA production and colitis protection. Mechanistically, CAA directly binds to the neutrophil receptor triggering receptor expressed on myeloid cells-1 (TREM1), thereby inhibiting neutrophil release of pro-inflammatory mediators and NETosis—pathological processes central to IBD progression. Finally, the therapeutic effect of CAA is completely abolished in neutrophil-specific Trem1 knockout (Trem1NeutKO) mice, confirming TREM1 as the critical target of CAA. This work establishes the C. sporogenes-CAA-TREM1 pathway as a promising therapeutic strategy for IBD.

Nanoparticle-based drug delivery system remains a significant challenge in the current treatment of solid tumors, primarily due to their limited penetration capabilities. Herein, we successfully engineer photodynamic gel-bombs (DCM@OPR) capable of penetrating deeply into tumor tissues utilizing the photodynamic-triggered explosive energy and receptor-mediated transcytosis, significantly enhancing the therapeutic efficacy of breast cancer. The photodynamic gel-bombs were fabricated by loading powerful components of chlorin e6 and MnO2 nanoparticles, as well as Doxorubicin, into a crosslinked Ca2+-gel. Upon exposure to laser irradiation, the obtained photodynamic gel-bombs are capable of generating explosive energy, resulting in their fragmentation into numerous nanofragments. The photodynamic-triggered explosive energy subsequently drives these nanofragments to deeply penetrate into tumor tissues through gap leakage among tumor cells. In addition, the photodynamic-triggered explosive energy also promotes the escape of those therapeutic components (including chlorin e6, MnO2 nanoparticles, and doxorubicin) and nanofragments from lysosomes. In the subsequent stages, these nanofragments also exhibit excellent transcytosis capacity, facilitating deep penetration into tumor tissues. As expected, the enhanced penetration and accumulation of therapeutic components into tumor tissues can be achieved, significantly enhancing the anti-proliferation capacity against breast cancer.

Current in vitro atherosclerosis (AS) models struggle to stimulate blood flow, limiting their ability to replicate endothelial injury and drug transport in AS development. To address this, we developed a 3-dimensional perfusable atherosclerotic vessel-on-a-chip (3D-PAVoC) platform that mimics vascular structure, blood circulating, and disease microenvironment. The system integrates endothelial cells and smooth muscle cells within a flow-enabled arterial construct, exposed to inflammatory (tumor necrosis factor-α and interleukin-1β) and hyperlipidemic stimuli (oxidized low-density lipoprotein) to recreate AS-prone conditions. Flow-dependent endothelial responses including enhanced cell growth and survival were observed, confirming the importance of hemodynamics in disease modeling. Then, rapamycin (RAP) was used as a model drug to evaluate therapeutic effects in the 3D-PAVoC. Compared to static vessel-on-a-chip models and conventional 2-dimensional cultures, 3D-PAVoC exhibited more pronounced AS pathology and higher RAP half-maximal inhibitory concentration, better reflecting in vivo conditions. The effective RAP dose identified in vitro was validated in apolipoprotein E knockout (ApoE−/−) mice, where it partially alleviated AS progression. Transcriptomic analysis revealed RAP-mediated modulation of AS-related gene functions and pathways. Overall, the 3D-PAVoC provides a physiologically relevant platform for anti-AS drug screening, bridging the gap between in vitro testing and in vivo validation, and offering insights into drug action under realistic vascular and pathological conditions.

BACKGROUND AND PURPOSE:Previous studies have reported that oral low-molecular-weight heparin (LMWH) ameliorated colitis by undefined mechanisms in ulcerative colitis (UC) patients. Our study explored the mechanisms of LMWH on colitis from the perspective of gut microbiota and its metabolites. EXPERIMENTAL APPROACH:Dextran sulfate sodium (DSS; 2.5%) was used to induce colitis in mouse model, and LMWH was administered by either oral gavage, intracolonic delivery or subcutaneous injection to compare their therapeutic effects. Pseudo-germ-free mice was established by using antibiotic cocktail, and faecal microbial transplantation (FMT) was performed to verify the role of microbiota in LMWH actions. Alcian blue staining, fluorescence in situ hybridization of EUB338 and immunohistochemical staining were performed to evaluate the integrity of gut mucus barrier. Amplicon sequencing, transcriptome sequencing and untargeted metabolome studies were used to explore LMWH mechanisms. The ameliorating effect of indole-3-propionic acid (IPA) was verified in vitro and in vivo. KEY RESULTS:Oral, but not subcutaneous, administration of LMWH alleviated colitis and enhanced the gut mucus barrier. Pseudo-germ-free mice and FMT assays confirmed that therapeutic effects of oral LMWH were dependent on gut microbiota. Oral LMWH increased Firmicutes abundance and decreased Escherichia/Shigella abundance, subsequently increasing microbial tryptophan metabolites, especially IPA. The protective effects of oral LMWH were reproduced by IPA supplementation, with mucus barrier enhancing through regulating the Wnt/β-catenin pathway. CONCLUSION AND IMPLICATIONS:The results provide new insights into the signalling mechanisms associated with the therapeutic potential of LMWH in colitis, and highlight the application of IPA for UC treatment.

The use of nanoparticles in nuclear medicine is paradoxical. While several nanoformulations, such as 99mTc colloids, have been used for diagnosis for decades, only a few new radionanomedicines have been able to reach the market, despite extensive preclinical efforts. This contradiction is dictated by the unique features of nanoparticles, such as (potential) prolonged circulation times, slow compartment exchanges, and large accumulations in the mononuclear phagocyte system, which allow for certain specific applications while preventing others. In this review, we discuss the development and clinical application of radiolabeled nanoparticles as imaging agents for disease diagnosis and patient stratification, as well as their promise and potential to be used as next-generation formulations to improve the efficacy of radiotherapy.

Rigid polyurethane foam (RPUF) is widely used for its lightweight and thermal insulation properties, but faces challenges of flammability and environmental impact from fossil-based raw materials. This study investigates cellulose-modified polyols as renewable additives to enhance RPUF performance [1-3]. Results show that hydroxyl-mediated crosslinking forms a rigid network, optimizing properties at 10 g addition: density 49.1 kg/m3, 23% higher compressive strength (0.18 MPa), 2.19% volume shrinkage, and limiting oxygen index (LOI) 24.3%. This formulation reduces reliance on traditional flame retardants, offering a green design strategy for polyurethanes.[4-5]

Timely endothelial regeneration and repair after stenting is essential for enhancing vascular healing performance. This necessitates that the stent surface be capable of maintaining a positive balance or sequential regulation among thrombosis, inflammation, and the growth behavior of smooth muscle cells (SMCs) and endothelial cells (ECs); however, a key challenge in achieving this goal remains. Herein, we report an immunomodulatory glutathione peroxidase (GPx) mimic-engineered α-lactalbumin self-assembling coating (LASC) for tailoring such surface multi-functionalities of a stent. The coating is achieved by first pre-coating an α-lactalbumin self-assembling nano-film driven by an oxidizing agent onto the stent surface, followed by covalent immobilization of GPx mimics (i.e., CuII-tetraazamacrocyclic (Cu-DOTA) coordination complexes) onto the LASC matrix. Cu-DOTA-engineered LASC (Cu-DOTA/LASC) exhibits potent GPx-mimicking catalytic activity, substantially resists adsorption by blood components, and stably and continuously decomposes S-nitrosothiols into nitric oxide (NO) in blood. The long-acting release of NO could create an endothelium-mimicking microenvironment to prevent thrombosis formation, regulate inflammation, inhibit SMC proliferation, and enhance EC growth. As a supplement to the functions of NO, the α-lactalbumin exhibited synergistic effects on anti-thrombosis and immunoregulation. In vivo studies demonstrate that the Cu-DOTA/LASC-functionalized stents enabled rapid re-endothelialization, hence effectively reducing stenosis.

Faecalibacterium prausnitzii (F. prausnitzii) has been recognized for its various intestinal and extraintestinal benefits to human. And reduction of F. prausnitzii has been linked to an increased risk of intestinal fibrosis in patients of Crohn’s disease (CD). In this study, oral administration of either live F. prausnitzii or its extracellular vesicles (FEVs) can markedly mitigate the severity of fibrosis in mice induced by repetitive administration of DSS. In vitro experiment revealed that FEVs were capable of directing the polarization of peripheral blood mononuclear cells (PBMCs) towards an M2b macrophage phenotype, which has been associated with anti-fibrotic activities. This effect of FEV was found to be stable under various conditions that promote the development of pro-fibrotic M1/M2a/M2c macrophages. Proteomics and RNA sequencing were performed to uncover the molecular modulation of macrophages by FEVs. Notably, we found that FEVs reprogramed every metabolism of macrophages by damaging the mitochondria, and inhibited oxidative phosphorylation and glycolysis. Moreover, FEV-treated macrophages showed a decreased expression of PPARγ and an altered lipid processing phenotype characterized by decreased cholesterol efflux, which may promote energy reprogramming. Taken together, these findings identify FEV as a driver of macrophage reprogramming, suggesting that triggering M2b macrophage polarization by oral admiration of FEV may serve as strategy to alleviate hyperfibrotic intestine conditions in CD.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, it is demonstrated that the adaptive microdrugs (even up to 3.0 µm in size) are more efficient than their nanodrugs (less than 200 nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibit enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. It is believed that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors.

Natural plants and traditional Chinese medicines (TCMs) have been widely used throughout human history and are available in many pharmaceutical markets. Plant-derived extracellular nanovesicles (PENVs), containing microRNAs, bioactive lipids, and proteins, serve as extracellular messengers to mediate cell-cell communication in a manner similar to those secreted by mammalian cells. PENVs participate in interspecies communication and may serve as natural therapeutic agents against various diseases, such as inflammatory diseases, liver diseases, and cancer. TCMs can induce changes by modulating the composition and surface factors of ENVs. Thus, these ENVs are closely related to TCM syndromes. ENVs derived from Chinese medicines could be used as biomarkers for clinical disease diagnosis, similar to microscopic syndrome differentiation in TCM syndrome differentiation and treatment. The unique design and transport capabilities of ENVs highlight their potential applications in drug delivery. In comparison with ENVs from mammalian cells, PENVs avoid the problems of unwanted genetic or protein transfer and detrimental immunogenic responses prior to clinical application. These features, coupled with the discovery of their intrinsic therapeutic effects, make PENVs ideal agents for drug delivery applications.

The presence of dense collagen fibers is a typical characteristic of triple-negative breast cancer (TNBC). Although these fibers hinder drug penetration and reduce treatment efficacy, the depletion of the collagen matrix is associated with tumor metastasis. To address this issue, epigallocatechin-3-gallate (EGCG) is first exploited for disrupting the dense collagenous stroma and alleviate fibrosis by specifically blocking the TGF-beta/Smad pathway in fibroblasts and tumor cells when intraperitoneally administrated in TNBC tumor-bearing mice. A methotrexate (MTX)-loaded dual phosphate- and pH-responsive nanodrug (pHA@MOF-Au/MTX) is next engineered by integrating Fe-based metal-organic frameworks and gold nanoparticles for improved chemo/chemodynamic therapy of TNBC. Surface modification with pH (low)-insertion peptide substantially enhanced the binding of the nanodrug to 4T1 cells owing to tumor stroma remodeling by EGCG. High-concentration EGCG inhibited glutathione peroxidase by regulating mitochondrial glutamine metabolism, thus facilitating tumor cell ferroptosis. Furthermore, sequential EGCG and pHA@MOF-Au/MTX treatment showed remarkable anti-tumor effects in a mouse model of TNBC, with a tumor growth inhibition rate of 79.9%, and a pulmonary metastasis rate of 96.8%. Altogether, the combination strategy developed in this study can improve the efficacy of chemo/chemodynamic therapy in TNBC and represents an innovative application of EGCG.