Search Results (2,119)

Background: Multidrug resistance (MDR), primarily driven by P-glycoprotein (P-gp)-mediated drug efflux, presents a significant challenge in cancer therapy, contributing to chemotherapy failure and poor patient outcomes. Objectives: In this study, we explored the potential of manidipine (MA), a clinically approved calcium channel blocker, to reverse P-gp-mediated MDR through modulation of calcium signaling via nuclear factor of activated T cells 2 (NFAT2). Methods: Paclitaxel (PTX) resistance ABCB1-overexpressing cancer in vitro and in vivo were used for evualting the anti-MDR effects of MA, as well as the underlying mechanism with siRNA of NFAT2. Results: We found that MA at non-toxic concentrations (0.6–5.4 μM) significantly sensitize drug-resistant colorectal (HCT-8/T) and non-small cell lung (A549/T) cells to PTX, reducing its IC₅₀ by up to 1328-fold in vitro models. Mechanistically, MA inhibited P-gp efflux activity without altering its expression, as shown by an increased intracellular accumulation of doxorubicin and Flutax-2 (2.3- and 3.1-fold, respectively) and dose-dependent modulation of ATPase activity (EC₅₀ = 4.16 μM). Notably, MA reduced intracellular calcium levels (52% reduction, p < 0.001) and downregulated NFAT2, an oncogene overexpressed in resistant cells. In vivo, MA (3.5 mg/kg) synergizes with PTX to inhibit tumor growth by 68% (p < 0.001) in A549/T xenograft model, without an observable decrease in weight. Conclusions: In sum, all these results position MA as a novel NFAT2 inhibitor to overcome P-gp-mediated MDR via modulating calcium signaling, which points to further investigation for its clinical applications. Full article

The design of innovative compounds displaying anti-inflammatory activity in oncological context is a subject of great interest in drug development. It has been proved that a pro-inflammatory microenvironment which accelerates cancer growth and cellular differentiation is often present in malignant bladder tumor. In earlier work, we reported the synthesis of p-aminobenzoic acid derivatives that act as anti-inflammatory compounds able to inhibit the pro-inflammatory markers present in bladder cancer microenvironment. DAB-1 rapidly emerged as an effective lead candidate in this investigation, with its ability to shrink by 90% in 25 days the size of human bladder cancer tumors in an ectopic mouse model. This manuscript discloses the synthesis of 23 new hydrazide derivatives of DAB-1 and reports their in vitro and in vivo biological evaluation. It was discovered that most of the new compounds are essentially nontoxic against RAW 264.7 cells, as evaluated by an MTT assay. Anti-inflammatory activity of the new derivatives was investigated by evaluation of their impact on cellular nitric oxide production, measured by a Griess assay. Some compounds did significatively inhibit nitric oxide production much more effectively than the original DAB-1. Striking activity of 14, which is around four times more potent than DAB-1, promotes this derivative as new lead compound in this study. The study of these analogs reveals that a phenolic/anisole core is a key component to achieve high biological activity. Furthermore, mice models of acute inflammation and invasive BCa tumors were used to assess the in vivo impact of derivative 14, and it was found that this compound does reduce inflammation in these mice, possess similar anti-inflammatory activity but higher anti-tumoral activity compared to DAB-1 with no apparent signs of toxicity. Full article

Colorectal cancer (CRC) remains a leading global health challenge, and natural products are increasingly explored for their multi-targeted therapeutic potential. Litchi chinensis seed extract (LCSE) has shown promising anti-cancer activity in vitro, though its in vivo effects remain underexplored. LCSE was analyzed by colorimetric assays and HPLC to quantify the phytochemical composition. Nude mice bearing HT-29 or SW480 xenografts were orally administered LCSE (0.1 or 0.6 g/kg) daily for 14 days. Tumor volume was measured, and immunohistochemistry was used to assess EGFR, p21, p53, Ki-67, CEA, CK20, CDX2, and Bax expression. Phytochemical profiling demonstrated LCSE contains abundant phenolics and flavonoids, with gallic acid as a predominant constituent, underscoring the potential bioactive properties. LCSE significantly inhibited tumor growth in HT-29 xenografts and dose-dependently reduced EGFR, p21, p53, cell cycle proteins and proliferation/differentiation markers. In SW480 tumors, inhibitory effects were evident primarily at the higher dose, with limited reduction in p53 expression. Bax levels remained unchanged in both models, indicating a non-apoptotic mechanism. No systemic toxicity was observed in treated mice. LCSE exhibits dose-dependent anti-tumor activity in CRC xenografts, likely mediated through suppression of proliferation and modulation of key regulatory proteins rather than apoptosis. These findings support LCSE as a safe, multi-target botanical candidate for CRC intervention and justify further mechanistic and translational studies. Full article

Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and a poor prognosis. Natural phytochemicals from Dendrobium species, particularly bibenzyl derivatives, possess diverse pharmacological activities, yet their potential against GBM remains largely unexplored. Here, we investigated the anticancer activity of 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB), a potent antioxidant bibenzyl derivative isolated from Dendrobium pachyglossum. In U87MG cells, TDB reduced viability in a dose- and time-dependent manner, suppressed clonogenic growth, induced apoptosis via Bax upregulation and Bcl-xL/Mcl-1 downregulation, and inhibited both mTORC1 and mTORC2 signaling. TDB also impaired cell migration and downregulated epithelial–mesenchymal transition (EMT)-associated proteins. Notably, TDB enhanced the cytotoxicity of temozolomide (TMZ), the current standard of care for GBM. These TMZ-sensitizing properties were further confirmed in patient-derived xenograft (PDX) Jx22 cells. To assess its potential for central nervous system delivery, blood–brain barrier (BBB) permeability was predicted using four independent in silico platforms—ADMETlab 3.0, LogBB_Pred, LightBBB, and BBB Predictor (Tree2C)—all of which consistently classified TDB as BBB-permeable. This predicted CNS accessibility, together with its potent anticancer profile, underscores TDB’s translational promise. Collectively, our findings identify TDB as a plant-derived antioxidant with multifaceted anti-GBM activity and favorable BBB penetration potential, warranting further in vivo validation and preclinical development as a novel therapeutic candidate for GBM. Full article

Background/Objectives: The ErbB protein family plays a critical role in the progression of various solid tumors, and HER3 has been implicated in resistance mechanisms to multiple cancer therapies due to its ability to form heterodimers with other ErbB receptors, thereby activating pathways that promote tumor growth and survival. This study aimed to generate and characterize humanized monoclonal antibodies against HER3 to inhibit its function and evaluate their potential as therapeutic agents. Methods: Murine monoclonal antibodies TK-A3 and TK-A4 were humanized and tested for binding to ErbB3 and competition with neuregulin-1β (NRG). Specificity was assessed by ELISA, and epitope identified by X-ray crystallography. Downstream signaling was analyzed by western blot for phosphorylated ErbB3, Akt, and MAPK. Antitumor activity was evaluated in vitro and in a pancreatic cancer xenograft model. A toxicology study was also conducted. Results: TK-hu A3 and TK-hu A4 bound specifically to ErbB3 without cross-reactivity to other ErbB receptors. The ErbB3-TK-hu A3 Fab structure revealed the binding epitope. Both antibodies competed with NRG, inhibiting ErbB3, Akt, and MAPK phosphorylation in a dose-dependent manner. They suppressed cancer cell survival in vitro, and TK-hu A3 significantly delayed tumor growth in vivo. The toxicology study indicated good tolerability. Conclusions: TK-hu A3 emerged as the lead candidate, showing specific HER3 targeting, strong pathway inhibition, and antitumor efficacy in vivo. Beyond standalone use, it could support novel strategies such as T-cell engagers, ADCs, CAR-T, and bispecific antibodies. These findings highlight TK-hu A3 as a promising therapy for HER3-positive, treatment-resistant cancers, meriting further development. Full article

Acute myeloid leukemia is characterized by the presence of malignant cells and their uncontrolled growth in bone marrow. Recent studies have been focused on the ability of curcumin, a polyphenol derived from the Curcuma longa plant. The role of curcumin is currently under investigation, due to its antitumor properties and action on several pathways, including Nuclear Factor kappa-light-chain-enhancer of activated B cells, Signal Transducer and Activator of Transcription 3, Phosphatidylinositol 3-kinase/protein kinase B, and mitogen-activated protein kinase. The aim of this review is to demonstrate the possible anti-leukemic effect of curcumin, thus its ability to induce apoptosis, inhibit cell proliferation, and modulate angiogenesis. Nowadays, although multiple synergistic effects have been observed and curcumin’s efficacy has been demonstrated through several in vivo and in vitro studies, further broad and exhaustive scientific research is needed to confirm the considerable results. In fact, the low bioavailability of curcumin has limited its clinical applications, a challenge that is currently being addressed through the development of nanoformulations to enhance its stability and absorption within the body. In conclusion, curcumin exhibits antitumor properties with a favorable profile, suggesting its potential as a supportive adjunct in the treatment of patients with acute myeloid leukemia. Full article

Background: Using natural substances for cancer therapy has attracted considerable interest due to their safety and reduced systemic toxicity. Nigella sativa (NS) oil, a traditional natural oil rich in bioactive compounds, possesses significant therapeutic potential. Brucine (BR), an alkaloid, exhibits potent cytotoxicity against various cancer cell lines; however, its poor selectivity and high systemic toxicity limit its clinical application. Objective: To overcome these challenges, this study aimed to enhance drug delivery and improve therapeutic efficacy. Method: A PEGylated nanoemulsion (NE) incorporating NS and BR was developed and characterized for particle size, size distribution, zeta potential, viscosity, and drug content. The in vitro release of BR was evaluated both with and without serum incubation. A quantitative amount of serum protein associated with the surface of the NE was estimated, and a hemolytic safety assay was carried out. Finally, an in vitro cytotoxicity study was conducted, and the in vivo anti-tumor effect of the developed PEGylated BR-loaded NE was evaluated and compared with its naked counterpart. Result: The developed PEGylated BR-loaded NE possessed favorable characteristics as a nanocarrier for parenteral administration, with a particle size of 188.5 nm, a zeta potential of −1.61, a viscosity of 3.4 cP, and 99% drug content uniformity. It released up to 60.4% of BR over 12 h, while only 18.4 µg/µmol of the total lipids were adsorbed on the surface of the formulation, compared with 54.5 µg/µmol for the naked counterpart. The PEGylated NE was safe, inducing less than 5% of hemolysis, and displayed substantial inhibition of MDA cell growth. Conclusions: The PEGylated NE achieved a significant reduction in tumor volume, suggesting that PEGylated NE may serve as a promising platform for enhancing anti-tumor activity. Full article

Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with limited therapeutic options despite multimodal treatment. Small interfering RNA (siRNA)-based therapeutics can silence tumor-promoting genes, but achieving efficient and tumor-specific delivery remains challenging. Lipid nanoparticles (LNPs) are promising siRNA carriers; however, conventional antibody conjugation can impair antigen recognition and complicate manufacturing. This study aimed to establish a modular Fc-binding peptide (FcBP)-mediated post-insertion strategy to enable PD-L1-targeted delivery of VEGF-siRNA via LNPs for GBM therapy. Methods: Preformed VEGF-siRNA-loaded LNPs were functionalized with FcBP–lipid conjugates, enabling non-covalent anchoring of anti-PD-L1 antibodies through Fc interactions. Particle characteristics were analyzed using dynamic light scattering and encapsulation efficiency assays. Targeted cellular uptake and VEGF gene silencing were evaluated in PD-L1-positive GL261 glioma cells. Anti-tumor efficacy was assessed in a subcutaneous GL261 tumor model following repeated intratumoral administration using tumor volume and bioluminescence imaging as endpoints. Results: FcBP post-insertion preserved LNP particle size (125.2 ± 1.3 nm), polydispersity, zeta potential, and siRNA encapsulation efficiency. Anti-PD-L1–FcBP-LNPs significantly enhanced cellular uptake (by ~50-fold) and VEGF silencing in PD-L1-expressing GL261 cells compared to controls. In vivo, targeted LNPs reduced tumor volume by 65% and markedly suppressed bioluminescence signals without inducing weight loss. Final tumor weight was reduced by 63% in the anti-PD-L1–FcBP–LNP group (656.9 ± 125.4 mg) compared to the VEGF-siRNA LNP group (1794.1 ± 103.7 mg). The FcBP-modified LNPs maintained antibody orientation and binding activity, enabling rapid functionalization with targeting antibodies. Conclusions: The FcBP-mediated post-insertion strategy enables site-specific, modular antibody functionalization of LNPs without compromising physicochemical integrity or antibody recognition. PD-L1-targeted VEGF-siRNA delivery demonstrated potent, selective anti-tumor effects in GBM murine models. This platform offers a versatile approach for targeted nucleic acid therapeutics and holds translational potential for treating GBM. Full article

Background/Objectives: Neuroblastoma (NB) is an aggressive pediatric malignancy that accounts for nearly 15% of all childhood cancer-related deaths, with high-risk cases showing a poor 20% prognosis and limited response to current therapies. Survivin, encoded by the BIRC5 gene, is an anti-apoptotic protein frequently overexpressed in NB and linked to treatment resistance and unfavorable clinical outcomes. Methods and Results: An analysis of 1235 NB patient datasets revealed a significant association between elevated BIRC5 expression and reduced overall and event-free survival, highlighting survivin as an important therapeutic target in NB. To explore this strategy, we evaluated the efficacy of YM-155, a small-molecule survivin inhibitor, across multiple NB cell lines. YM-155 displayed potent cytotoxic activity in six NB cell lines with IC₅₀ values ranging from 8 to 212 nM and significantly inhibited colony formation and 3D spheroid growth in a dose-dependent manner. Mechanistic analyses revealed that YM-155 downregulated survivin at both mRNA and protein levels, induced apoptosis by about 2–7-fold, and caused G0/G1 phase cell cycle arrest. Moreover, YM-155 treatment enhanced p53 expression, suggesting reactivation of tumor suppressor pathways. Notably, combining YM-155 and the chemotherapeutic agent etoposide resulted in synergistic inhibition of NB growth with ED75 values ranging from 0.17 to 1, compared to either agent alone. In the xenograft mouse model, YM-155 inhibited tumor burden in contrast to controls by about 3-fold, and without any notable toxic effects in vivo. Conclusion: Overall, our findings identify YM-155 as a promising therapeutic agent for high-risk NB by directly targeting survivin and enhancing chemosensitivity. These results support continued preclinical development of survivin inhibitors as part of rational combination strategies in pediatric cancer treatment. Full article

Background: Hepatocellular carcinoma (HCC) is a highly lethal malignancy with limited therapeutic options. Arctigenin (ARC), a natural lignan derived from Saussurea medusa, exhibits anti-cancer activity, but its mechanism against HCC remain incompletely elucidated. Methods: This study integrated network pharmacology, molecular docking, molecular dynamics, in vitro, and in vivo experiments to investigate ARC’s anti-HCC effects. Results: Seventy-five potential targets shared between ARC and HCC were identified, with KEGG analysis highlighting the PI3K/AKT pathway as central. ARC showed strong binding to key proteins, and molecular dynamics indicated stable interactions with PIK3CA and GSK3B. In HepG2 cells, ARC inhibited proliferation in a dose- and time-dependent manner (IC50: 11.17 μM at 24 h, 4.888 μM at 48 h), induced apoptosis at high concentrations, suppressed PIK3CA phosphorylation, and increased GSK3B (Ser9) phosphorylation. In H22 tumor-bearing mice, ARC dose-dependently inhibited tumor growth (high dose: 50.6% vs. 63.0% for CTX) with minimal weight loss. Conclusions: These findings suggest ARC suppresses HCC by modulating the PI3K/AKT pathway, providing evidence for its development as a plant-derived therapeutic agent. Full article

Background/Objectives: Chimeric Antigen Receptor (CAR)-T cell therapy has demonstrated impressive clinical results against hematological malignancies. However, currently commercialized CAR-T therapies are designed for autologous use, which entails some disadvantages, including high costs, manufacturing delays, complex standardization, and frequent production failures due to patient T cell dysfunction. Moreover, their CARs target one specific antigen, increasing the probability of antigen-negative tumor relapses. To overcome these limitations, we developed a novel NKG2D CAR-T cell therapy for allogeneic use with broad target specificity, as this CAR targets eight different ligands commonly upregulated in both solid and hematological tumors. Additionally, the manufacturing process was optimized to improve the phenotypic characteristics of the final product. Methods: Multiplex CRISPR/Cas9 technology was applied to eliminate the expression of TCR and HLA class I complexes in healthy donor T cells to reduce the risk of graft-versus-host disease and immune rejection, respectively, as well as lentiviral transduction for introducing the second-generation NKG2D-CAR. Moreover, we sought to optimize this manufacturing process by comparing the effect of different culture interleukin supplementations (IL-2, IL-7/IL-15 or IL-7/IL-15/IL-21) on the phenotypic and functional characteristics of the product obtained. Results: Our results showed that the novel CAR-T cells effectively targeted cervicouterine and colorectal cancer cells, and that those manufactured with IL-7/IL-15/IL-21 supplementation showed the most suitable characteristics among the conditions tested, considering genetic modification efficiency, cell proliferation, antitumor activity and proportion of the stem cell memory T cell subset, which is associated with enhanced in vivo CAR-T cell survival, expansion and long-term persistence. Conclusions: In summary, this new prototype of NKG2D CAR-T cell therapy for allogeneic use represents a promising universal treatment for a wide range of tumor types. Full article

Colorectal cancer (CRC) remains a major contributor to global cancer-related mortality, with rising incidence observed in several regions, including Saudi Arabia. This review compiles and critically analyzes recent preclinical research from Saudi-based institutions that investigates the anti-CRC potential of natural and synthetic compounds. Numerous natural products such as Nigella sativa, Moringa oleifera, Curcuma longa, and marine-derived metabolites have demonstrated cytotoxic effects through pathways involving apoptosis induction, reactive oxygen species (ROS) generation, and inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and cyclooxygenase-2 (COX-2). In parallel, synthetic and semi-synthetic agents, including C4–G4 (semi-synthetic hybrids designed from flavonoids and benzoxazole scaffolds that act as dual epidermal growth factor receptor (EGFR)/COX-2 inhibitors)), oxazole derivatives, and camptothecin-based nanocarriers, exhibit promising anti-tumor activity via molecular targeting of cyclin-dependent kinase 8 (CDK8), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and β-catenin pathways. Selected in vivo studies primarily utilizing xenograft and chemically induced rodent models have shown reductions in tumor volume and modulation of apoptotic and inflammatory biomarkers. Additionally, green-synthesized metallic nanoparticles (NPs) and polyethylene glycol (PEG)-modified carriers have been investigated to improve bioavailability and tumor targeting of lead compounds. While these findings are encouraging, the majority remain in preclinical phases. Limitations such as poor solubility, lack of pharmacokinetic data, and absence of clinical trials impede translational progress. This review highlights the need for standardized evaluation protocols, mechanistic validation, and region-specific clinical studies to assess efficacy and safety. Given Saudi Arabia’s rich biodiversity and growing research capacity under national strategies like Vision 2030, the country is well-positioned to contribute meaningfully to CRC drug discovery. By integrating bioactive natural products, rationally designed synthetics, and advanced delivery platforms, a pipeline of innovative CRC therapeutics tailored to local and global contexts may be realized. Full article

Despite numerous research efforts and several effective vaccines and therapies developed against coronavirus disease 2019 (COVID-19), drug repurposing remains an attractive alternative approach for treatment of SARS-CoV-2 variants and other viral infections that may emerge in the future. Cellular polyamines support viral propagation and tumor growth. Here we tested the antiviral activity of two polyamine metabolism-targeting drugs, an irreversible inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), and a non-steroidal anti-inflammatory drug (NSAID), Sulindac, which have been previously evaluated for colon cancer chemoprevention. The drugs were tested as single agents and in combination in the human Calu-3 lung adenocarcinoma and Caco-2 colon adenocarcinoma cell lines and the K18-hACE2 transgenic mouse model of severe COVID-19. In the infected human cell lines, the DFMO/Sulindac combination significantly suppressed SARS-CoV-2 N1 Nucleocapsid mRNA by interacting synergistically when cells were pretreated with drugs and additively when treatment was applied to the infected cells. The Sulindac alone and DFMO/Sulindac combination treatments also suppressed the expression of the viral Spike protein and the host angiotensin-converting enzyme 2 (ACE2). In K18-hACE2 mice, the antiviral activity of DFMO and Sulindac as single agents and in combination was tested as prophylaxis (drug supplementation started 7 days before infection) or as treatment (drug supplementation started 24 h post-infection) at the doses equivalent to patient chemoprevention trials (835 ppm DFMO and 167 ppm Sulindac). The drugs’ antiviral activity in vivo was evaluated by measuring the clinical (survival rates and clinical scores), viral (viral load and virus infectivity), and biochemical (plasma polyamine, Sulindac, and Sulindac metabolite levels) endpoints. Prophylaxis with DFMO and Sulindac as single agents significantly increased survival rates in the young male mice (p = 0.01 and p = 0.027, respectively), and the combination was effective in the aged male mice (p = 0.042). Young female mice benefited the most from the prophylaxis with Sulindac alone (p = 0.001) and the DFMO/Sulindac combination (p = 0.018), while aged female mice did not benefit significantly from any intervention. Treatment of SARS-CoV-2-infected animals with DFMO or/and Sulindac did not significantly improve their survival rates. Overall, our studies demonstrated that DFMO and Sulindac administration as the prophylaxis regimen provided strong protection against the lethal outcome of SARS-CoV-2 infection and that male mice benefited more from the polyamine-targeted antiviral treatment than female mice. Our findings underscore the importance of evaluation of the antiviral activity of the drugs in the context of sex and age. Full article

Snack bars are convenient, ready-to-eat foods with various natural ingredients and may serve as functional foods, offering bioactive phytochemicals. In this study, tomato-based snack bars enriched in plant proteins were evaluated for their antioxidant, antidiabetic, anti-obesity, and anti-inflammatory properties by in vitro test, comparing different protein sources (pea and RuBisCO) and drying methods (microwave vacuum and oven). The rubisco bars exhibited the highest levels of polyphenols (10.12 ± 0.27 mg GAE/g) and flavonoids (5.65 ± 0.47 mg CE/g), and demonstrated superior antioxidant capacity in DPPH, ORAC, and FRAP assays, particularly when microwaved. Rubisco bars also exhibited better inhibition activity of dipeptidyl-peptidase IV and pancreatic lipase, suggesting potential antidiabetic and anti-obesity effects. In contrast, pea bars displayed notable anti-inflammatory effects by reducing tumor necrosis factor (TNF)-α-induced cyclooxygenase-2 (COX-2) expression in intestinal cells. Both protein types were digestible, though rubisco bars released more peptides during simulated gastrointestinal digestion. While these in vitro findings provide insights into the functional potential of tomato-based snack bars, further studies, including in vivo investigations, are required to confirm their health-promoting effects and to evaluate physiologically relevant doses. Overall, these findings highlight the potential of tomato-based snack bars as sustainable, nutrient-rich functional foods with potential health-promoting properties. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) exhibits pronounced biological heterogeneity, aggressive behavior, and a high risk of recurrence and metastasis. The conventional treatments for TNBC have notable limitations: surgical resection may leave residual tumor cells; chemotherapy (CT) frequently induces systemic toxicity and drug resistance; and radiotherapy damages surrounding organs and compromises the patients’ immune function. Methods: Herein, we designed a carrier-free nanodrug delivery system composed of self-assembled Curcumin nanoparticles (NPs) coated with a tannic acid (TA)/Fe(III) network (denoted as CUR@TA-Fe(III) NPs). We systematically evaluated the in vitro cytotoxicity and photothermal–ferroptosis synergistic therapeutic efficacy of CUR@TA-Fe(III) NPs in 4T1 breast cancer cells, as well as the in vivo antitumor activity using 4T1 tumor-bearing mouse models. Results: CUR@TA-Fe(III) NPs had high drug loading efficiency (LE) of 27.99%, good dispersion stability, and photothermal properties. Curcumin could inhibit the growth of 4T1 cancer cells, while TA-Fe(III) efficiently converted light energy into heat upon exposure to near-infrared (NIR) light, leading to direct thermal ablation of 4T1 cells. Additionally, TA-Fe(III) could supply Fe(II) via TA, increase intracellular Fe(II) content, and generate reactive oxygen species (ROS) through the Fenton reaction, in turn inducing lipid peroxidation (LPO), a decrease in mitochondrial membrane potential (MMP), and glutathione depletion, eventually triggering ferroptosis. Conclusions: This treatment strategy, which integrates CT, PTT, and ferroptosis, is expected to overcome the limitations of traditional single-treatment methods and provide a more effective method for the treatment of TNBC. Full article