Tri-Modal Anticancer Therapy via Mo ₂ C-MXene-Based Hybrid Nanostructures: A Synergistic Strategy Against Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive tumor subtype that is resistant to conventional therapies due to the lack of targetable receptors. In this study, a paclitaxel (PTX)-loaded Mo₂C@C@Fuc/Mo₂C-MXene@Fuc hybrid nanosystem was developed, and the efficacy of a combined therapeutic approach, photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy (CT) was evaluated <i>in vitro</i> and <i>in vivo</i> against TNBC. The PTX/Mo₂C@C@Fuc/Mo₂C-MXene@Fuc hybrid nanosystem exhibited high drug loading efficiency and stimuli-responsive release. At 96 h, PTX release reached 58.6% at pH 4.5 and 44.2% at pH 6.0, while NIR irradiation further enhanced the release to 66.3% and 51.0%, respectively, confirming the pH- and light-responsive drug delivery capability of the system. Under NIR irradiation (808 nm), the hybrid structure generated significant levels of reactive oxygen species (ROS), leading to pronounced apoptotic induction and reducing cell viability to 52.8% in 4T1 cells. Similarly, in MDA-MB-231 cells, NIR-assisted combination treatment decreased viability to 55.9%. In contrast, L929 normal fibroblast cells retained a viability of 75.4% under the same treatment conditions, indicating cytotoxicity. Tube formation assay results demonstrated that the hybrid system significantly inhibited vascular structure formation in HUVEC cells after 24 h of incubation. <i>In vivo</i> studies further confirmed that the PTX-loaded hybrid system combined with NIR irradiation induced 82% necrosis and 12.5% apoptosis within tumor tissues, ultimately resulting in complete macroscopic tumor regression. Overall, this study highlights the potential of Mo₂C-MXene-based hybrid nanostructures as a biocompatible and therapeutic platform for synergistic PDT/PTT/CT combination therapy in TNBC treatment.