Search Results (1,125)

Lactic acid accumulates in the tumour microenvironment (TME) at concentrations reaching up to 40 mM. Initially, lactic acid was considered merely a metabolic by-product of aerobic glycolysis, a phenomenon commonly referred to as the Warburg effect and observed in the majority of tumours. Recent evidence, however, has demonstrated that lactic acid is not merely a waste product; rather, it plays a pivotal role in tumour biology. High plasma lactic acid levels correlate with increased metastatic potential and lower survival rates. Elevated lactic acid levels in the TME have been shown to suppress antitumour immune responses, facilitate both metastasis and cellular senescence, and might modulate gene expression through novel epigenetic mechanisms such as histone lactylation. This review aims to summarize current knowledge on the multifaceted impact of elevated lactic acid in the TME on tumour progression and biology. Full article

Amaryllidaceae alkaloids are of notable pharmacological relevance. For instance, galanthamine is used in the treatment of Alzheimer’s disease, while other alkaloids (lycorine, crinine, etc.) derived from Amaryllidaceae plants are also of great interest because they exhibit antitumour, antiviral, antibacterial, antifungal, antimalarial, analgesic and cytotoxic properties. Phenolic acids comprise a group of natural bioactive substances that have commercial value in the cosmetic, food and medicinal industries due to their antioxidant, anticancer, anti-inflammatory and cardioprotective potential. In the present study, the effect of temperature (15, 20, 25 and 30 °C) on Amaryllidaceae alkaloid and phenolic acid biosynthesis in Leucojum aestivum in vitro plant cultures was investigated. The highest diversity of alkaloids (i.e., galanthamine, crinan-3-ol, demethylmaritidine, crinine, 11-hydroxyvitattine, lycorine, epiisohaemanthamine, chlidanthine) was noted in plants cultured at 30 °C. By contrast, ismine and tazettine were only present in plants cultured at 15 °C. Temperatures of 20 °C and 30 °C were found to stimulate galanthamine accumulation. The highest lycorine content was noted in plants grown at temperatures of 15 and 30 °C, and it was negatively correlated with the expression of the gene that encodes the cytochrome P450 96T (CYP96T) enzyme which catalyses a key step in the biosynthesis of different types of Amaryllidaceae alkaloids. This observation may reflect temperature-induced shifts in metabolic flux among different branches of Amaryllidaceae alkaloid biosynthesis. The observed stimulating effect of a 15 °C temperature on the chlorogenic, caffeic, p-coumaric, sinapic, ferulic and isoferulic acid content was in line with the highest expression of a gene that encodes the tyrosine decarboxylase (TYDC) enzyme, which is involved in plant stress response mechanisms. At 30 °C, however, the highest content of the caffeic, vanillic, p-coumaric and isoferulic acids was noted. Full article

Background. Glucocorticoid-induced osteoporosis represents a well-known type of secondary osteoporosis (SOp). While the most prevalent sub-category includes corticotherapy, another important contributor is represented by Cushing’s syndrome. In this traditional landscape, adrenal incidentalomas do not involve a standard cause of SOp, since most of them are non-functioning adrenal tumours (NFATs). Yet, 30–40% of them are not entirely “non-functioning”, due to mild autonomous cortisol secretion (MACS). Despite not being a guideline-based diagnosis, a lower ACTH might point to various NFATs/MACS complications. Objective. This study aimed to determine the relationship between the bone health status of post-menopausal women with NFATs/MACS and their baseline morning ACTH level. The bone health indicators were DXA, FRAX, and bone remodelling markers. Methods. This was a retrospective, real-life, transversal study in adult females who were hospitalized in a single tertiary centre of endocrinology. They were all anti-osteoporotic drug-naïve. The subjects underwent CT and DXA scanning and a 1 mg dexamethasone suppression test (DST). Results. The cohort (sample size of N = 84 patients, 61.49 ± 7.86 years) had a type 2 diabetes rate of 18%, arterial hypertension rate of 75%, and a dyslipidemia rate of 78%. Median ACTH was 11.89 pg/mL. The prevalence of MACS was 30.95%. The mean largest tumour diameter (LTD) was 2.25 ± 0.99 cm. ACTH correlated with second-day cortisol after the 1 mg DST (r = −0.301, p = 0.024), and LTD (r = −0.434, p < 0.001). ROC analysis for the bone resorption marker CrossLaps showed an AUC of 0.647 (p = 0.05), with the highest Youden index for the cut-off at 0.32 ng/mL (sensitivity 87.50%, specificity 39.50%). Bone impairment (osteoporosis + osteopenia) was found in 65% of patients, with an osteoporotic fracture prevalence of 4.76%. The lowest mean T-score (−1.12 ± 1.00) showed osteopenia, and the median trabecular bone score pointed a partially degraded microarchitecture [median (interquartile interval): 1.320 (1.230, 1.392)]. FRAX and FRAXplus estimations correlated with bone mineral density (BMD) at all three central DXA sites, regardless of the ACTH cut-off. Patients with a low ACTH (<10 pg/mL) displayed similar bone/adrenal features when compared to those with normal ACTH, except forbut they had a higher MACS rate (45.45% versus 21.57%, p = 0.021) and a larger LTD (2.67 ± 0.98 versus 1.98 ± 0.92 cm, p = 0.003). Fracture estimation showed that only in patients with a low ACTH, the 10-year fracture risk for major osteoporotic fractures (MOF) adjusted for lumbar BMD was lower than the risk for MOF adjusted for diabetes (p = 0.036), and the 10-year hip fracture risk was lower when adjusted for lumbar BMD (p = 0.007). ACTH correlated with lumbar BMD (r = 0.591, p = 0.002) only in the group with an ACTH < 10 pg/mL, suggesting its potential usefulness as a bone biomarker in these cases. On the other hand, MACS-negative subjects with a low ACTH versus those with a normal ACTH showed higher CrossLaps (0.60 ± 0.27 versus 0.42 ± 0.21 ng/mL, p = 0.022), indicating an elevated bone resorption even in patients with tumours that are regarded as true non-secretors. Conclusions. A subgroup of patients diagnosed with NFATs/MACS might be prone to skeletal damage, and biomarkers such as ACTH (specifically, suppressed ACTH) might serve as a surrogate pointer to help refine this higher risk in daily practice. Further research to address other ACTH cut-offs will place ACTH assays in the overall bone status evaluation in these patients, most probably not as a single biomarker, but in addition to other assays. Full article

(1) Cancer has been shown to contribute to the progression of atherosclerosis, while inflammatory aspects of atherosclerosis can exert profound effects on cancer development and outcomes. TA-MUC1 (Tumour-associated Mucin 1) is a transmembrane glycoprotein that is overexpressed in many human epithelial cancers lining the intestine. Interestingly, the lack of intestinal MUC1 has been shown to impair cholesterol uptake in MUC1^−/− mice. (2) To investigate whether TA-MUC1 could have specific effects on cholesterol metabolism and, thereby, have the potential of impacting the pathogenesis of atherosclerosis in cancer patients. (3) The effect of TA-MUC1 on cholesterol and lipid metabolism was assayed using MUC1 gene knock down breast cancer cells. An in vitro coculturing model similar to in vivo biological conditions was used to determine that TA-MUC1 could also modulate the cholesterol metabolism of other cells. (4) Reduction or inhibition of TA-MUC1 activity resulted in a significant alteration in a number of the signalling pathways and proteins that are relevant to abnormal cholesterol metabolism (p < 0.0001). Coculturing of TA-MUC1 cancer cells with THP-1 cells also notably effectively induced monocytic THP-1 cell differentiation towards foam cells—foam cells being a characteristic feature of atherosclerotic blood vessels. (5) Previously, we found TA-MUC1 downregulation led to a reduction in procoagulant and prothrombotic properties of the cancer cells as well as modulation of the aberrant calcium signalling pathways of cancer cells. Taken together with these current results, this suggests that TA-MUC1 in cancer cells has multiple effects on cholesterol and lipid metabolism, which also impacts other cells in the cellular bioenvironment. TA-MUC1 could thereby act as an important pathogenic effector of atherosclerosis in cancer. These results can also be considered in respect of the therapeutic anti-MUC1 antibody, which was able to reduce the effect of TA-MUC1 on cholesterol metabolism. Modulation of cholesterol metabolism via targeting TA-MUC1 could, therefore, be of great benefit to cancer patients with atherosclerosis. Full article

Gliomas, particularly glioblastoma multiforme, remain among the most lethal brain tumours despite multimodal therapy. Increasing evidence indicates that systemic factors, including the gut microbiota, may influence glioma progression through immune, metabolic, and neurochemical pathways. We conducted a comprehensive systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to synthesize recent evidence on the role of gut and intratumoral microbiota in glioma biology. Peer-reviewed studies published within the last five years were identified through structured searches of major biomedical databases, and original studies using human cohorts, animal models, or Mendelian randomization approaches were included. The 17 studies met the eligibility criteria. Glioma was consistently associated with gut dysbiosis characterized by a reduced Firmicutes:Bacteroidetes ratio and enrichment of Verrucomicrobia, particularly Akkermansia, alongside decreased short-chain fatty acids and altered neurotransmitter profiles, contributing to neuroinflammation, immune suppression, and blood–brain barrier dysfunction. Antigenic mimicry by Bacteroidetes-derived peptides may impair antitumour T-cell responses, while intratumoral Fusobacteriota and Proteobacteria appear to promote angiogenesis and pro-inflammatory chemokine expression. In contrast, SCFA-producing taxa such as Ruminococcaceae and probiotic genera including Lactobacillus and Bifidobacterium show protective associations. Evidence is limited by small cohorts and methodological heterogeneity. Standardized humanized models and integrated multi-omics approaches are required to clarify causal mechanisms and support microbiome-targeted therapies in glioma. Full article

Background/Objectives: Interactions between colorectal tumours and their immune microenvironment critically influence disease progression and response to immunotherapy. However, most organoid systems fail to preserve the complex architecture and immune composition of the original tissue. Here, we applied the air–liquid interface (ALI) organoid model to paired tumour and perilesional colon tissues from colorectal cancer patients to evaluate its ability to retain immune and genetic features and to reproduce responses to chemotherapy and immune checkpoint blockade. Methods: Fresh human tumour and matched healthy colon tissues were processed to generate ALI organoids. Their histological organization, immune cell composition (including CD45⁺ subsets), and genomic profiles were compared with those of the parental tissues and with conventional Matrigel organoids, either alone or co-cultured with peripheral blood mononuclear cells (PBMCs). Organoids were exposed to 5-FU and nivolumab (anti–PD-1) to assess local immune modulation. Results: ALI organoids faithfully preserved the three-dimensional architecture, native immune infiltrates, and somatic mutational landscape of the source tissues. Importantly, upon PD-1 blockade with nivolumab, ALI organoids consistently exhibited a local expansion of regulatory T cells (Tregs), a phenomenon that could contribute to adaptive immune resistance. This response was not reproduced in PBMC–Matrigel co-culture systems, highlighting the importance of preserving endogenous tumour–immune interactions. Conclusions: Patient-derived ALI organoids represent a physiologically relevant platform that conserves key structural, immunological, and genomic hallmarks of colorectal cancer. By capturing clinically relevant immune remodeling events, such as Treg expansion following PD-1 blockade, this model provides a powerful tool for dissecting tumour–immune interactions. Full article

The field of nanotechnology has witnessed a paradigm shift towards eco-friendly and sustainable synthesis methods for nanoparticles due to increasing concerns over environmental toxicity and resource sustainability. Among various metal oxide nanoparticles, zirconium dioxide (ZrO₂) nanoparticles have garnered significant attention owing to their exceptional thermal stability, biocompatibility, mechanical strength, and catalytic properties. Doping ZrO₂ with transition metals such as copper (Cu) further enhances its physicochemical attributes, including antibacterial activity, redox behaviour, and electronic properties, rendering it suitable for a diverse range of biomedical and industrial applications. In the present study, we report the green synthesis of copper-doped ZrO₂ nanoparticles (Cu-ZrO₂-CO NPs) using an aqueous extract of Calendula officinalis (marigold) flowers as a natural reducing and stabilizing agent. The complete characterization was performed using UV–vis spectrophotometry, dynamic light scattering (DLS), zeta potential, FTIR, SEM, EDAX, and XRD, revealing its size to be around 20–40 nm and zeta potential as −20 mV, indicating nano size and stability. The biocompatibility of the as-synthesized nanoparticle was analyzed in vitro using fibroblast cell viability and haemolysis assay, and in vivo using brine shrimp assay. The nanoparticles were safe up to a dose of 50 μg/mL, showing more than 95% cell viability and less than 2% haemolysis, which is within an acceptable range. Finally, the anticancer activity was explored for A549 cells by MTT assay and live-dead assay, with an IC50 value of 38.63 μg/mL. The chorioallantoic membrane (CAM) model was used to assess the anti-angiogenesis potential of the Cu-ZrO₂-CO NPs. The results showed that the nanoparticles could kill the cancer cells via apoptosis, and one of the reasons for the anticancer effect was angiogenesis inhibition. Further research is needed using other cancer cell lines and animal tumour models. Full article

Curcumin has anti-tumour and antibacterial effects. In this research, fourteen kinds of piperidone monocarbonyl curcumin analogues with 3,5-dimethylene-4-piperidone as the parent scaffold and halogen substitution on both sides of the benzene ring were synthesized by Claisen–Schmidt reaction, and their anti-tumour effect, mechanism, and antibacterial activity were investigated. It was found that a series of curcumin analogues has different degrees of anti-tumour and antibacterial dual activity. Among them, 2,5-2Cl, 2Br-5Cl, 2-Cl, 2-F, and benzaldehyde have strong broad-spectrum anti-tumour effects and have obvious selective inhibitory effects on A549 cells. The IC₅₀ value is less than 5 μmol/L. The five promising compounds, respectively, inhibited the expression of AKT and ERK to induce apoptosis of A549 cells to varying degrees. The newly synthesized analogues 2,5-2Cl and 2Br-5Cl had stronger inhibitory effects on the growth of A549 cells than other analogues, and they tended to mainly inhibit the expression of AKT and ERK, respectively. However, 2-Cl and 2-F have significantly better inhibitory effects on methicillin-resistant Staphylococcus aureus (MRSA) than antibiotics. Taken together, piperidone monocarbonyl curcumin analogues may be developed as good candidates for potential prevention and treatment of cancer and bacterial infection complications. Full article

Background/Objectives: AXL, a receptor tyrosine kinase of the TAM family, has emerged as a key target in cancer therapy due to its role in tumour growth, metastasis, immune evasion, and therapy resistance. SLC-391, a novel, orally bioavailable and selective AXL inhibitor, has demonstrated potent anti-tumour effects in preclinical studies. This first-in-human, open-label, multi-centre Phase I clinical trial (NCT03990454) was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of SLC-391 in patients with advanced solid tumours. Methods: Using a 3 + 3 design, SLC-391 was administered orally, either once daily (from 25 mg up to 175 mg QD) or twice daily (from 75 mg to 200 mg BID) in 21-day cycles. Results: Following single and repeated dosing, SLC-391 was generally well tolerated by subjects. The maximum tolerated dose (MTD) was not reached in this study. A total of 34/35 subjects experienced at least one TEAE. Three (8.6%) subjects experienced Grade 3 TRAEs that were considered related to SLC-391. Eight SAEs were reported in five (14.3%) subjects (seven Grade 3 SAEs and one Grade 2 SAE), in 150 mg QD (3/6, 50%), 175 mg QD (1/2, 50%), and 110 mg BID (1/3, 33.3%) cohorts. Four SAEs in three (8.6%) subjects led to dose interruption, drug withdrawal, or study discontinuation. Three DLTs were reported in two subjects: one subject experienced Grade 3 hematochezia (SUSAR/DLT) at 175 mg QD, and another subject experienced Grade 3 thrombocytopenia associated with Grade 1 hematuria at 200 mg BID. The median T_max was 2.0 h. Plasma concentrations following multiple doses generally increased with higher doses and appeared to reach steady state by Day 21 and were generally dose-proportional. Twelve (12) out of 35 subjects with solid tumours achieved stable disease according to RECIST or mRECIST (mesothelioma), with durations of stable disease lasting up to 318 days on SLC-391 monotherapy. The clinical benefit rate was 34.3%. Conclusions: This first study of SLC-391 in adult subjects with advanced solid tumours demonstrated that a total daily dose of 300 mg (150 mg BID) of SLC-391 monotherapy was generally well tolerated, with no DLTs or SAEs observed at this dose. The drug’s promising safety profile, along with stable disease reported for several subjects with advanced solid tumours, provides a strong rationale for the phase 1b/2a clinical investigation of SLC-391 in combination with pembrolizumab in subjects with advanced or metastatic non-small cell lung cancer (NSCLC) (NCT05860296). Full article

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a small neuropeptide detected first in the hypothalamo–hypophyseal system; recently, it has also been identified in peripheral organs and in tumours. It is well demonstrated that PACAP exerts cell- and tissue-protecting effects in various stressful conditions and helps to maintain tissue homeostasis. In melanoma, the anti-invasive effect of PACAP has been demonstrated; however, there is also existing sporadic data which proves PACAP plays a role in melanoma progression. The major goal of our study was to investigate the signalling targets of PACAP in A2058 and WM35 melanoma cell lines in vitro. Various molecular players of melanocyte differentiation and function responded to PACAP application. SOX9 expression increased while SOX10 expression decreased and CREB signalling did not change. The expression level of TYRP1 decreased, while DCT elevated, and MITF expression showed changes at the mRNA level and in its subcellular localisation. In contrast, the amount of hyaluronan (HA) and expressions of its synthases, as well as RHAMM, increased, indicating the role of PACAP in secretion of an HA-rich matrix. In parallel with these results, we detected elevated hyaluronidase2 (Hyal2) expression in the presence of PACAP. On the other hand, alfaV and beta3 integrin expressions did not alter significantly. Our results demonstrate that exogenous PACAP modulates the expression of multiple target molecules in melanoma cells. Some of the significantly responding molecules take part in hyaluronan homeostasis, suggesting an effect of PACAP on tumour matrix composition, through which it can modulate invasiveness of melanoma cells. Full article

HER2 (human epidermal growth factor receptor 2) is a receptor tyrosine kinase which is overexpressed in ~20% of patients with oesophagogastric adenocarcinoma (EGA). HER2 represents a targetable transmembrane glycoprotein receptor of the epidermal growth factor receptor (EGFR) family, which plays a crucial role in cell proliferation, survival, and differentiation. HER2 significantly influences the tumour microenvironment (TME) through various mechanisms, creating a niche that supports tumour progression, immune evasion, and therapeutic resistance. In HER2-positive EGA, aberrant signalling pathways, such as PI3K/AKT and MAPK/ERK, enhance tumour cell survival and proliferation, whilst upregulation of angiogenic factors like VEGF fosters vascularization, meeting a tumour’s metabolic demands and facilitating its proliferation. HER2 also modulates the tumour immune microenvironment (TIME) by downregulating MHC molecules and recruiting immunosuppressive cells, including regulatory T-cells (T-reg) and tumour-associated macrophages (TAMs), which release cytokines that further inhibit anti-tumour immune responses. Together, these factors foster a pro-inflammatory, immunosuppressive microenvironment that underpins resistance to HER2-targeted therapies. As more HER2-directed treatments become available, such as trastuzumab–deruxtecan (T-DXd), gaining a deeper understanding of the multifaceted influence of HER2 on the TME in EGA will be crucial for the development of improved targeted treatments that can overcome these challenges and lead to advancements in targeted treatment for HER2-overexpressing EGA. This review provides a comprehensive overview of the impact of HER2 on the TME in EGA and highlights the challenge it represents as well as the opportunity for novel therapeutic development and the implications for patients in terms of clinicopathological outcomes. Full article

Penile cancer (PeCa) is a rare malignancy with few validated tissue biomarkers to guide prognosis and treatment, despite growing evidence for a key role of inflammation in its biology. This retrospective study evaluated whether the immuno-expression of selected pro-inflammatory cytokines is associated with disease progression and cancer-specific survival (CSS) in PeCa. Immunohistochemistry (IHC) analysis of eight cytokines (IL-1A, IL-1B, IL-2, IL-6, IL-12, TGF-β1, TNF-α and IFN-γ) was performed in paired tumour tissues and corresponding negative surgical margins from 94 patients with penile squamous cell carcinoma. Compared with surgical margins, tumour tissues showed a characteristic inflammatory shift, with markedly increased IL-1β and IL-6 and relatively reduced TNF-α, IFN-γ, IL-12 and IL-2. Receiver Operating Characteristic (ROC) analysis indicated that TNF-α, IL-6 and IL-12 had the strongest ability to discriminate tumour from normal tissue and provided data-driven cut-offs for subsequent analyses. Within tumour samples, high IL-1α, IL-12 and TGF-β1 immuno-expression was significantly associated with advanced UICC TNM prognostic stage and lymph node involvement. Importantly, in contrast to the classically anti-tumour role of IL-12 described in many other solid cancers, increased IL-12 immuno-expression in tumour tissues in our cohort was independently associated with poorer CSS in multivariable Cox regression (HR 2.42, 95% CI: 1.08–5.41, p = 0.031), alongside advanced TNM stage (HR 5.03, 95% CI: 2.12–11.95, p = 0.0002). These findings highlight IL-1α, IL-12 and TGF-β1 as promising tissue biomarkers of aggressive PeCa and support a central role for cytokine-driven immune dysregulation in penile cancer. The prognostic value of IL-12 should be considered exploratory and warrants validation in larger, multicentre cohorts. Full article

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy accounting for 3% of adult cancers globally. Despite advances in immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF)-targeted therapies, durable disease control remains elusive for many patients. Increasing evidence implicates the acidic tumour microenvironment (TME) as a critical mediator of RCC progression, immune evasion, and therapeutic resistance. Solid tumours, including RCC, exhibit reversed pH gradients, characterised by acidic extracellular (pH 6.2–6.9) and alkaline intracellular conditions. This dysregulation arises from enhanced glycolysis, hypoxia-driven lactate accumulation, and the overexpression of pH-regulating enzymes such as carbonic anhydrase (CA9). Acidic TMEs impair cytotoxic T-cell and NK-cell activity, promote tumour-associated macrophage (TAM) polarisation towards an immunosuppressive phenotype, and upregulate alternative immune checkpoints. These mechanisms collectively undermine ICI efficacy and contribute to primary and secondary treatment resistance. Proton-sensing G-protein-coupled receptors (GPCRs), notably GPR65, have emerged as pivotal mediators linking extracellular acidosis to immune dysfunction. Preclinical studies demonstrate that GPR65 antagonists restore anti-tumour immune activity by reversing acidosis-driven immunosuppression and enhancing antigen processing. In RCC models, selective GPR65 inhibitors have shown the ability to reduce immunosuppressive cytokine IL-10 production, induce immunoproteasome activation, and synergise with anti-PD-1 therapy. The first-in-class GPR65 inhibitor, PTT-4256, is now under evaluation in the Phase I/II RAISIC-1 trial (NCT06634849) in solid tumours, including RCC. Targeting acid-sensing pathways represents a novel and promising therapeutic strategy in RCC, aiming to remodel the TME and overcome ICI resistance. Integrating GPR65 inhibition with existing immunotherapies may define the next era of RCC management, warranting continued translational and clinical investigation. Full article

Small interfering RNAs (siRNAs) have emerged as a powerful tool in the treatment of aggressive cancers. By exploiting and mimicking the natural gene regulation mechanism of RNA interference (RNAi), they allow for sequence-specific silencing of aberrant genes. siRNA-mediated knockdown of the inflammatory cytokine tumour necrosis factor-alpha (TNF-α) presents a novel therapy for triple-negative breast cancer (TNBC). This study investigated the potential of novel biomimetic glutathione-synthesised gold nanoclusters (AuNCs) as siRNA delivery vehicles. AuNCs were functionalized with biocompatible chitosan and polyethene glycol, and their interactions with siRNAs were investigated through binding studies. In vitro cytotoxicity and cellular uptake were conducted in the human breast cancer (MCF-7), TNBC (MDA-MB-231), and embryonic kidney (HEK293) cells, while the effect of anti-TNF-α siRNA nanocomplexes on biological processes, such as oxidative stress, apoptosis, and cell cycle distribution, was investigated using flow cytometry. UV–visible and Fourier transform infrared spectroscopy, as well as transmission electron microscopy, confirmed the synthesis and functionalization of the AuNCs. Functionalized AuNCs (FAuNC) effectively bound and condensed siRNA and protected against nuclease degradation. AuNCs facilitated efficient cellular uptake and were well-tolerated in vitro. Anti-TNF-α siRNA treatment of the MDA-MB-231 cells increased apoptosis and oxidative stress levels, and affected cell cycle distribution. Although the overall knockdown was low, these FAuNCs exhibited favorable physicochemical characteristics, low cytotoxicity and good cellular uptake in vitro, warranting further optimisation for improved delivery of therapeutic siRNAs. Full article