Search Results (2,877)

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with persistent disparities in stage at diagnosis. While transportation-related exposures are increasingly recognized as environmental health risks, the biological mechanisms linking these exposures to cancer progression remain unclear. This study evaluated whether tumor microRNAs (miRNAs), which regulate gene expression and tumor behavior, mediate the association between transportation burden and TNBC stage at diagnosis. Methods: We analyzed 434 TNBC cases from the Louisiana Tumor Registry (2009–2019). The transportation burden from the 2022 Environmental Justice Index reflects the residential proximity to high-volume roads, railways, and airports. miRNA expression was measured via high-throughput sequencing and normalized using the trimmed mean of M-values method. Three-phase analysis (screening, individual, and multiple mediation) was performed. KEGG pathway enrichment analysis assessed downstream biological pathways. Results: After adjusting for age, race, body mass index, marital status, primary payer, and concentrated disadvantage index (CDI), every 0.10 (10-percentile) increase in transportation burden rank was significantly associated with a 9% increase in the odds of late-stage TNBC diagnosis (Adjusted OR = 1.09, 95% CI: 1.01–1.17, p = 0.021). Five miRNAs significantly mediated this relationship: downregulated hsa-let-7c-5p, hsa-let-7b-5p, hsa-miR-30a-3p, and hsa-miR-92a-3p, and upregulated hsa-miR-151a-3p. Joint mediation analysis demonstrated complete mediation (indirect effect = 0.324; p = 0.027). hsa-let-7c-5p was the primary independent mediator. The enriched pathways included MAPK, PI3K-Akt, Wnt, and p53 signaling. Conclusions: These findings identified molecular pathways linking transportation-related environmental exposures to TNBC progression through dysregulation of miRNAs. By integrating environmental exposure assessment with tumor biology, this study advances our understanding of how the built environment contributes to cancer disparities. Full article

Background: The diversity of RNA isoforms plays a critical role in regulating the development and progression of human cancers. Our previous work has demonstrated that piR-2158 exerts antitumor activity in breast cancer by repressing IL11-STAT3 signaling. Methods: The isoforms of piR-2158 were analyzed using Sanger sequencing, quantitative real-time PCR (qRT-PCR), and Gene Expression Omnibus (GEO) dataset. Cell proliferation capacity was assessed using Cell Counting Kit-8 (CCK-8) assays and Ki67 immunofluorescence staining. Cell migration was evaluated using wound healing assays. Cancer cell stemness was analyzed using mammosphere formation assay, stemness marker detection, and ALDH activity assay. Results: We identified two types of piR-2158 isoforms in mammary tissues: a 31 nt long isopiR (designated as iso-piR-2158-L) and a 28 nt short isopiR (designated as iso-piR-2158-S). Predominant expression of iso-piR-2158-L was observed in normal mammary epithelial cells and adjacent non-tumor breast tissues, whereas it was significantly downregulated in TNBC cell lines and primary tumor tissues. We experimentally demonstrated that iso-piR-2158-L and iso-piR-2158-S exert distinct effects on TNBC cell proliferation, migration, and stemness, with iso-piR-2158-L showing significantly stronger antitumor effects than iso-piR-2158-S. Subsequent mechanistic studies revealed that iso-piR-2158-L suppresses IL11 expression more effectively, compared to iso-piR-2158-S. Conclusions: Our findings reveal a piRNA isoform-based regulatory pathway that may be involved in regulating pathological transformation, tumor initiation, and progression in TNBC. Full article

Experimental evidence has shown that gallic acid (GA), a naturally occurring polyphenolic compound, and docetaxel (DTX), a taxane chemotherapeutic agent, each possess antitumor activity against multiple cancer types. Although both compounds have been investigated individually, their combined effects in triple-negative breast cancer (TNBC) have received limited attention, and the molecular basis of their interaction remains unclear. The present study examined the in vitro effects of GA and DTX in MDA-MB-231 TNBC cells while simultaneously assessing their comparative cytotoxicity in HaCaT human keratinocytes. Evaluation of treatment efficacy included measurement of cell viability by the MTT assay and assessment of drug interactions using the Chou–Talalay combination index (CI) method. Apoptosis together with cell-cycle distribution was subsequently examined using both Annexin V/PI flow cytometry and TALI^® image-based cytometry. Additional analyses included β-tubulin immunofluorescence (IF), caspase-9 immunocytochemistry, ELISA, wound-healing assays, quantitative real-time PCR, and bioinformatic analyses to investigate treatment-associated biological alterations. Combined exposure to GA and DTX produced a significant reduction in cell viability and exhibited synergistic activity in MDA-MB-231 cells. The coordinated biological response to the combined treatment was characterized by increased apoptotic cell death, arrest of the cell cycle at the G2/M phase, extensive disorganization of the β-tubulin network, and enhanced caspase-9 immunoreactivity. Beyond its effects on cell survival, the combined regimen substantially decreased the release of IL-6, IL-8, and TNF-α, limited wound-healing capacity, and reshaped the expression profile of the apoptosis- and cell cycle-related genes BCL2, BAX, CASP9, and CDKN1A. Bioinformatic analyses further revealed enrichment of apoptosis- and cell-cycle-associated pathways that were generally consistent with the experimental observations. The overall pattern of experimental responses indicates that combining GA with DTX enhances the in vitro antitumor efficacy of DTX in TNBC cells by simultaneously influencing apoptotic pathways, cell-cycle regulation, inflammatory cytokine secretion, and cellular migratory capacity. Although the bioinformatic findings provide supportive hypothesis-generating evidence, additional studies using three-dimensional models, in vivo experiments, and functional validation approaches are necessary to confirm the underlying molecular mechanisms and to further define the translational potential of this therapeutic combination. Full article

Breast cancer is a highly heterogeneous malignancy with multiple molecular subtypes and variable treatment responses. Despite advances in endocrine therapy, HER2-targeted therapy, chemotherapy, and immunotherapy, treatment resistance and disease recurrence remain major clinical challenges. There is growing evidence that transcriptional plasticity and enhancer relinking contribute to tumor progression and treatment adaptation, highlighting the powerful role of epigenetic regulators. CREB-binding protein (CBP) and E1A-associated protein p300 (EP300) are transcriptional coactivators that regulate breast cancer enhancer activity and lineage-specific gene expression. Emerging research suggests that CBP/p300 is more of a context-dependent vulnerability point than a universal carcinogenic driver. ER-positive tumors exhibit a strong dependence on CBP/p300-mediated transcriptional programs, while the triple-negative breast cancer subgroup, including androgen receptor-positive and immunosuppressive tumors, may rely on CBP/p300-dependent signaling to maintain survival and treatment resistance. This is in contrast to their role in HER2-positive breast cancer. This review summarizes the biological functions of CBP/p300 in breast cancer and discusses subtype-specific vulnerability, biomarker-directed patient stratification, drug resistance mechanisms, rational combination strategies, and current translational challenges, emphasizing the need for precise treatment of breast cancer. Full article

Chemotherapy resistance in triple-negative breast cancer (TNBC) remains a critical clinical challenge, with a substantial proportion of patients failing to achieve pathological complete response following neoadjuvant chemotherapy (NAC). Using an integrative single-cell RNA sequencing (scRNA-seq), bulk transcriptomic, and spatial proteomic framework, we aimed to identify the malignant epithelial subset driving this resistance and the intercellular signaling axes through which it reprograms the tumor microenvironment (TME). scRNA-seq analysis of NAC-treated breast tumors revealed a Fatty Acid–EMT co-expressing epithelial subset (FA-EMT) that is selectively enriched in the chemotherapy-resistant residuum. Critically, FA-EMT co-expression—rather than either program individually—most powerfully predicted chemotherapy resistance and reduced overall survival across two independent bulk transcriptomic cohorts comprising 277 TNBC patients (p < 0.001). CellChat ligand–receptor analysis established FA-EMT cells as the dominant TME signaling hub, deploying MDK–NCL and MIF–CD74–CXCR4 axes to simultaneously suppress adaptive and innate anti-tumor immunity via T-cell exhaustion, Treg activation, and the expansion of myeloid-derived suppressor cells. Spatial CyCIF validation in a published paclitaxel-resistant TNBC mouse model (n = 69 cores) confirmed significant Metabolic-EMT enrichment in resistant tumor cores (p = 0.0085) with physical co-localization with immunosuppressive MDSC and Treg populations. These findings establish the FA-EMT subset as a key cellular driver of treatment failure in TNBC and nominate MDK–NCL and MIF–CD74–CXCR4 as mechanistically grounded therapeutic targets with the potential to dismantle the FA-EMT-driven immunosuppressive niche and sensitize chemotherapy-resistant TNBC to cytotoxic treatment. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes and remains associated with limited therapeutic options and high systemic toxicity from conventional chemotherapy. Ipomoea pes-caprae is a coastal medicinal plant traditionally consumed in Mexico for inflammatory and renal disorders and contains bioactive metabolites with reported antioxidant and pharmacological properties. However, its antitumoral activity and systemic safety profile remain poorly understood. This study aimed to characterize the phytochemical composition, antioxidant capacity, antitumoral activity, and toxicity of a traditionally prepared aqueous infusion of I. pes-caprae leaves (IPCAE). Methods: IPCAE was characterized using phytochemical screening and complementary instrumental analyses. Antioxidant activity was evaluated using the DPPH assay. A randomized preclinical study was performed in mice bearing MDA-MB-231 xenografts treated with IPCAE, cisplatin, or saline control. Results: The infusion showed measurable antioxidant activity (72.25 ± 1.25% DPPH inhibition at 1 mg/mL) and a total polyphenol content of 7.29 µg/mg gallic acid equivalents. Phytochemical screening revealed abundant flavonoids and reducing sugars, with moderate saponin content. In vivo, IPCAE produced only a transient and non-significant trend toward slower tumor progression compared with control (p = 0.214) and cisplatin (p = 0.377). However, marked systemic toxicity was observed, including severe thoracic dermal lesions in 40% of animals and 70% mortality by day 15. Survival was significantly reduced compared with control and cisplatin groups (p < 0.001). Conclusions: Although IPCAE exhibited antioxidant activity, no statistically significant antitumoral effect was observed under the evaluated conditions. Furthermore, repeated oral administration resulted in marked systemic toxicity, characterized by visible dermal lesions, clinical deterioration, and increased mortality. Therefore, the present findings do not support the use of the evaluated crude preparation as an anticancer intervention. Future studies should focus on detailed toxicological characterization, bioassay-guided fractionation, dose optimization, and identification of the individual metabolites responsible for the observed biological effects. The antioxidant activity demonstrated in this study should be interpreted independently from antitumoral activity, as no causal relationship between these findings was established. Full article

Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen, progesterone, and HER2 receptors; an aggressive phenotype; high rates of early relapse and metastasis; and the worst mortality rates among all breast cancer subtypes. Currently, there is no effective curative targeted therapy for TNBC and chemotherapy remains the primary treatment for TNBC. Therefore, there is a critical need to develop highly effective, novel therapies to improve patient survival. We previously validated FOXM1, a proto-oncogenic transcription factor, for the first time as a potential molecular target in TNBC through genetic knockdown studies in mice. We show that FOXM1 expression is associated with shorter patient survival and is a marker of poor prognosis. There is no FDA-approved FOXM1 inhibitor. We found that patients with TP53 mutations have dramatically higher FOXM1 expression, indicating that widespread TP53 mutations detected in about 80% of TNBC patients are the major driver of FOXM1 overexpression in TNBC patients. We identified its binding ability using an in silico study, and found it to be a well-known FOXM1 inhibitor that suppresses TNBC cell proliferation, migration, and invasion, and induces apoptosis. In vivo studies in mice bearing TNBC tumors demonstrated that treatment with a novel FOXM1 inhibitor incorporated in single-lipid nanoparticles suppressed the growth of TNBC tumor xenografts. In conclusion, our findings suggest that the novel FOXM1 inhibitor represents a potent and safe therapeutic strategy with significant potential for the treatment of other FOXM1-driven cancers including TNBC that currently have limited treatment options. Full article

Spatially resolved single-cell technologies can provide deep insights into cellular heterogeneity and tissue structural characteristics. However, the data obtained are purely observational and cannot reveal the specific mechanisms by which tissues respond to particular perturbations. Most computational models of single-cell perturbations either operate in a non-spatial latent space or fix tissue geometry within a static spatial structure, thereby limiting their ability to integrate molecular profiles with tissue topological remodeling. We propose SPAD-CFR (Spatial Point-cloud Attention-based Diffusion for CounterFactual Reprogramming). Each tissue is treated as a spatial point cloud containing cellular molecular profiles and physical coordinates. We implement Pearl’s three-step workflow for causal inference through deterministic diffusion inversion and sampling. This model can apply interventions to individual cells and generate counterfactual-style tissues in which molecular profiles and spatial coordinates change together. In validation across three datasets, SPAD-CFR reproduces the hierarchical structure of the mouse cerebral cortex, simulates phenotypic distribution differences across different histological grades of breast cancer, and reconstructs hypoxia-associated mesenchymal phenotypes at the invasion margins of triple-negative tumors. In melanoma, activation interventions targeting PD-1+ CD8+ T cells produce spatially confined, distance-dependent bystander cytotoxic effects. Based on these findings, we propose SPAD-CFR, a biologically informed generative framework for conducting counterfactual-style spatial simulations to validate hypotheses regarding microenvironment reprogramming. Full article

Background: Pembrolizumab-containing regimens have become the standard of care across the spectrum of triple-negative breast cancer (TNBC). While their use in the neoadjuvant setting is independent of biomarker status, their application in metastatic disease remains strictly contingent upon PD-L1 expression. Given that PD-L1 prevalence can vary significantly by ethnicity and geography, the lack of specific data for the Mexican population creates a challenge for optimizing treatment in the metastatic setting. This study sought to characterize PD-L1 positivity rates in a Mexican TNBC cohort to better define the local molecular landscape. Methods: We conducted a retrospective study across two cancer centers in Mexico to assess PD-L1 positivity in a cohort of women with TNBC (stages I–IV) diagnosed between 2006 and 2021. PD-L1 expression was assessed and evaluated centrally using the 22C3 pharmDx assay, with a Combined Positive Score (CPS) of ≥1 considered positive. We explored the association between PD-L1 expression and clinicopathological features. Results: Of the 298 TNBC patients identified, 285 (96%) had sufficient tissue for CPS evaluation and thus were included in the analysis. PD-L1 positivity was observed in 29.1% of the cohort, and 13.3% of patients had a CPS ≥ 10. PD-L1 positivity was associated with higher histological grades (91.3% vs. 78.5%, p = 0.035) and TILs ≥ 30% (22.2% vs. 10.0%, p = 0.007). Additionally, pre-treatment surgical specimens were more frequently PD-L1 positive than tumor biopsies (56.6% vs. 30.7%, p < 0.001). Conclusions: This study characterizes the PD-L1 landscape in Mexican women with TNBC, reporting a 29.1% prevalence of CPS ≥ 1. The strong association between PD-L1 positivity and high TILs/histological grade highlights the role of the immune microenvironment in these aggressive phenotypes. Given the significant variability observed between specimens (biopsy vs. surgical), clinicians should consider the dynamic nature of PD-L1 expression when choosing treatment strategies. Full article

Stress MAPKp38γ (MAPK12) has established roles in promoting tumorigenesis; however, the mechanisms involved remain largely unclear. This paper will review recently published and unpublished studies of p38γ in programming immune evasion in breast cancer, pancreatic cancer, and colon cancer to promote tumorigenesis. First, we show that p38γ is an oncogene that transforms breast epithelial cells into triple-negative breast cancer (TNBC), is required for breast tumorigenesis in mice, and activates tumor-suppressive environments via a positive feedback signaling loop. Moreover, we show that epithelial p38γ is required for KRAS-oncogene-induced pancreatic cancer in two genetic murine models (KPC and KTC) by activating glycolytic pathways to provide metabolic support for cancer cells and by increasing chemokine CXCL5-dependent fibrosis and immune cell infiltrations. Lastly, we will delineate how p38γ is activated by the main risk factors for colon cancer and serves as a key integrator of oncogenic and inflammatory signaling to promote tumorigenesis by increasing Wnt proliferative signaling and programming immune evasion. These results indicate that p38γ MAPK can integrate common risk factors for colon cancer and amplify oncogenic signaling by phosphorylating its substrate, β-catenin, increasing transcription of Wnt and the chemokine CXCL13, and promoting PD-L1 expression. In each of these tumor models, we will present evidence supporting our hypothesis, followed by additional experiments for verification. Our studies suggest that targeting p38γ may be an innovative approach in cancer therapeutic intervention. Full article

Vasculogenic mimicry (VM) is a non-endothelial mode of tumor vascularization in which aggressive cancer cells form vessel-like networks that support microcirculation, metastasis, and resistance to anti-angiogenic therapies. VM is particularly prominent in triple-negative breast cancer (TNBC), but its molecular regulators remain incompletely understood. Focal adhesion kinase (FAK) and its paralog, proline-rich tyrosine kinase 2 (Pyk2), are closely related non-receptor tyrosine kinases implicated in epithelial-to-mesenchymal transition (EMT), invasion, and metastasis in TNBC. However, their roles in VM have not been defined. Here we perform transcriptomic analysis of FAK and Pyk2 clinical expression patterns using TNMplot V2, DepMap, and patient cohort datasets to systematically dissect the distinct contributions of FAK and Pyk2 to VM in TNBC. Our in vitro tube formation assay shows that in TNBC cells, knockdown of FAK, but not Pyk2, results in failure to form robust 3D vessel-like networks in Matrigel. Similarly, overexpression of Pyk2, but not FAK, in TNBC cells results in poor vessel-like network formation. Consistent with these findings, analysis of two independent patient cohorts (TCGA-BRCA and METABRIC) revealed selective upregulation of FAK in TNBC, while Pyk2 was inversely associated with vasculogenic-mimicry-associated gene expression, supporting the opposing roles of the two kinases in patient tumors. Taken together, these findings establish that FAK and Pyk2 govern VM through non-redundant, kinase-specific, and functionally opposed mechanisms: FAK acting as a positive regulator of VM, and Pyk2 as a context dependent suppressor of VM at elevated levels. These results nominate FAK as a candidate target for suppressing VM-driven tumor perfusion in TNBC and suggest that dual FAK/Pyk2 inhibition warrants caution hypotheses that remain to be tested pharmacologically. Full article

Triple negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer characterized by the absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), resulting in limited options for targeted therapy and high rates of metastasis, recurrence and death. Extracellular vesicles (EVs) have emerged as central mediators of TNBC pathophysiology, functioning as key intercellular communication vehicles transporting oncogenic proteins, nucleic acids, lipids, and metabolites. These EV-mediated interactions promote tumor microenvironment (TME) remodeling, immune evasion, metastatic niche formation, and therapeutic resistance. Given their stability, accessibility, and molecular complexity, EVs also represent promising diagnostic and prognostic biomarkers for TNBC. Advances in isolation and molecular profiling technologies have enabled the identification of EV-associated signatures that predict therapeutic response and stratify patient risk. Beyond their utility as biomarkers, EVs are rapidly emerging as therapeutic targets and delivery platforms, demonstrating efficacy in transporting chemotherapeutics, RNA-based therapeutics, immune modulators, and photosensitizers with enhanced targeting specificity and therapeutic efficiency. Collectively, EVs play a multifaceted role in TNBC biology, serving simultaneously as drivers of disease progression, minimally invasive biomarkers, and versatile therapeutic vehicles. The integration of EV-centered diagnostics, multi-omic profiling, and engineered therapeutics holds significant potential to transform TNBC management and advance precision oncology for this challenging breast cancer subtype. Full article

Background: Comparative oncology uses naturally occurring cancers in companion animals to study tumor biology and therapeutic responses relevant to human cancer. Spontaneous feline tumors are increasingly recognized as useful comparative models because they arise in immunocompetent hosts, develop under shared environmental exposures, and can reproduce selected clinical, histopathologic, molecular, and therapeutic features of human malignancies. Methods: This review compares feline oral squamous cell carcinoma (FOSCC) with human head and neck squamous cell carcinoma (HNSCC), and feline mammary carcinoma (FMC) with human breast cancer, emphasizing shared pathologic, molecular, tumor microenvironment, and therapeutic features. Results: Recent immunohistochemical, genomic, transcriptomic, and biomarker studies have identified shared features between feline and human cancers. FOSCC resembles human HNSCC through aggressive local invasion, histologic features, therapeutic resistance, and recurrent alterations of TP53, MYC, and PTEN. FMC shows strong overlap with aggressive human triple-negative breast cancer, including reduced hormone receptor expression, recurrent TP53, PIK3CA, and CXCL12/CXCR4 signaling alterations, and tumor microenvironment features involving immune-checkpoint, inflammatory, and angiogenic pathways. FOSCC clinical trials and emerging clinical investigations into FMC treatments further support the use of cats for translational therapy evaluation. Conclusions: FOSCC and FMC are promising comparative oncology models for human HNSCC and aggressive breast cancer, respectively. Future multicenter studies incorporating standardized tumor classification and grading, predefined stratification criteria, and clinically meaningful endpoints will be essential to strengthen their translational value. Full article

Triple-negative breast cancer (TNBC), particularly when associated with breast cancer susceptibility gene 1/2 (BRCA1/2) alterations or homologous recombination deficiency (HRD), remains therapeutically challenging because DNA repair vulnerabilities coexist with molecular heterogeneity, resistance, and toxicity constraints. This narrative review synthesizes mechanistic, preclinical, clinical, and translational evidence on DNA damage response (DDR)-targeted and synthetic lethality-based strategies in TNBC. We summarize TNBC biological heterogeneity, current biomarker-guided treatment options, mechanisms of poly(ADP-ribose) polymerase (PARP) inhibition and resistance, and emerging DDR targets, including ataxia telangiectasia and Rad3-related/checkpoint kinase 1 (ATR/CHK1), WEE1, DNA-dependent protein kinase (DNA-PK), RAD51, DNA polymerase theta (POLQ), neddylation-related pathways, and targeted protein degradation. The review highlights that PARP inhibitors and platinum agents provide clinically validated examples of exploiting HRD in selected populations, whereas most next-generation DDR inhibitors remain preclinical, investigational, or in early clinical trials. Resistance mechanisms, including BRCA reversion, homologous recombination restoration, replication fork stabilization, and checkpoint adaptation, limit durable benefit. Safety, target selectivity, overlapping toxicities, and the lack of standardized functional biomarkers further constrain translation. Future progress will require prospective biomarker validation, dynamic HRD assessment, rational scheduling of combinations, and medicinal chemistry approaches that improve therapeutic index rather than a broad application of DDR inhibition across all TNBC. Full article

Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling residual disease. Doxorubicin (DOX), although widely used, shows limited tumor selectivity, considerable systemic toxicity, and poor control over drug release at the tumor site. To address these issues, we developed near-infrared (NIR)-responsive gold-decorated phase-change nanodroplets (AuNPs-DOX-NDs) that combine photothermal conversion, liquid-to-gas phase transition, and controlled DOX release in a single platform. Methods: The nanodroplets consisted of a perfluorohexane (PFH) core, a DOX-loaded lipid shell, and polyethyleneimine-modified gold nanoparticles (PEI-AuNPs) conjugated to the surface as the NIR photothermal component. Physicochemical characterization was performed to evaluate morphology, colloidal dispersity, and storage stability. Under 808 nm laser irradiation, the photothermal behavior, PFH vaporization, and DOX release properties of AuNPs-DOX-NDs were investigated. In vitro studies using 4T1 TNBC cells were conducted to assess intracellular DOX accumulation, cell proliferation, migration, and apoptosis. Results: Physicochemical characterization showed that the nanodroplets had a uniform nanoscale morphology, good colloidal dispersity, and acceptable storage stability. Under 808 nm laser irradiation, AuNPs-DOX-NDs exhibited concentration-dependent photothermal heating, which induced PFH vaporization and accelerated DOX release, indicating a clear stimulus-responsive release behavior. In vitro studies using 4T1 TNBC cells showed enhanced intracellular DOX accumulation after treatment with AuNPs-DOX-NDs. Upon laser irradiation, the nanodroplets further inhibited cell proliferation and migration and promoted apoptosis, suggesting an enhanced combined photothermal–chemotherapeutic effect in 4T1 TNBC cells. Conclusions: These results indicate that AuNPs-DOX-NDs may serve as a useful NIR-responsive platform for externally controlled drug release and enhanced combined photothermal-chemotherapy, and deserve further evaluation in vivo. Full article