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.

The presence of nanopollutants in the atmosphere poses significant risks to human health. However, research on their adverse effects on the central nervous system (CNS) remains limited. To address this gap, we constructed an in vitro model utilizing mesoporous silica nanoparticles (MSNs) to simulate airborne solid particulates and menthol/curcumol to represent adsorbed liquid microparticles. This model was employed to investigate the impact of nanopollutants on the CNS, focusing on their entry pathways into the CNS and the mechanisms underlying their cellular transport and uptake. The results showed that airborne MSNs could enter the CNS through direct and indirect pathways. Furthermore, co-exposure to liquid microparticles (menthol and curcumol) enhanced the entry of MSNs into the CNS. It was shown that MSNs mixed with curcumol and menthol disrupted certain cellular tight protein components and cell membrane surface integrity. Curcumol and menthol adsorbed onto MSNs also reduced cellular stiffness. Lysosomal co-localization analysis revealed minimal association of intracellular MSNs with lysosomes, suggesting limited biodegradation of these solid and liquid microparticles by lysosomal enzymes following cellular internalization.