The development of smart, selective, and multifunctional nanotherapeutics is crucial for advancing next-generation cancer treatments. In this study, superparamagnetic iron oxide nanoclusters (SPIONCs) were coated with mesoporous silica, functionalized with folic acid (FA), and co-loaded with curcumin (CUR) and capecitabine (CAPE) to create a novel nanocarrier system. To enhance cellular internalisation, magnetophoresis was applied before exposure of the cells to cold atmospheric plasma (CAP). The resulting FA-conjugated, CUR and CAPE-loaded nanoclusters were evaluated in vitro in MCF-7 breast cancer and HME-1 normal epithelial cells at varying CAP exposure durations (0, 10, and 20 s) and incubation times (24 and 48 h). This is the first report demonstrating the co-loading of CUR and CAPE into FA-functionalised mesoporous silica-coated magnetic nanoclusters. Drug release studies revealed significantly enhanced release profiles under acidic conditions (pH 5.0 and 6.5), mimicking lysosomal and tumour microenvironments, compared to physiological pH (7.4). Drug-loaded nanoclusters exhibited substantially higher cytotoxicity than the controls with no loading, with a more pronounced effect in MCF-7 cells. Notably, the combined treatment of CAP and CUR-CAPE loaded NCs showed a synergistic cytotoxic effect. IC₅₀ values, after 10 s CAP exposure and 24 h incubation, decreased to 0.43 µg mL⁻¹ for MCF-7 cells and 37 µg mL⁻¹ for HME-1 cells. The elevated levels of reactive oxygen species (ROS) induced by CAP played a key role in the observed cytotoxic effects, and both CUR and CAPE were found to enhance this process through ROS-related and potentially additional molecular pathways. These findings highlight the potential of CAP-assisted multicomponent nanocarriers as a promising platform for effective cancer therapy.

Aim: Anticancer drugs (chemotherapeutics) used in cancer treatment (chemotherapy) lead to drug resistance. This study was conducted to investigate the possible effect of iron on calcium homeostasis in epithelial ovarian cancer cells (MDAH-2774) and cisplatin-resistant cells of the same cell line (MDAH-2774/DDP). Methods: To develop MDAH-2774/DDP cells, MDAH-2774 (MDAH) cells were treated with cisplatin in dose increases of 5 μM between 0 μM and 70 μM. The effect of iron on the viability of MDAH and MDAH/DDP cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test at the end of 24 h incubation. Results: At increasing iron concentrations in MDAH and MDAH/DDP cells, the mRNA gene of fifteen genes [inositol 1,4,5-triphosphate receptor (IP3R)1/2/3, ryanodine receptor (RYR)1/2, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)1/2/3, Na+/Ca2+ exchange (NCX)1/2/3, and plasma membrane Ca2+ ATPase (PMCA)1/2/3/4] associated with Ca2+ differences in expression were determined by quantitative reverse transcription-polymerase chain reaction. Changes in IP3R2, RYR1, SERCA2, NCX3, PMCA1, and PMCA3 gene expressions were observed in iron treatment of MDAH/DDP cells, while changes were detected in iron treatment of MDAH cells in IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX2/3, and PMCA1 expressions. Conclusions: This changes in the expression of calcium channels, pumps, and exchange proteins in the epithelial ovarian cancer cell line and in cisplatin-resistant epithelial ovarian cancer cells suggest that iron may have an important role in regulating calcium homeostasis. Due to differences in the expression of genes that play of an important role in the regulation of calcium homeostasis in the effect of iron, drug resistance can be prevented by introducing a new perspective on the use of inhibitors and activators of these genes and thus cytostatic treatment strategies.

Photodynamic therapy (PDT) is a reactive oxygen species (ROS)-based treatment modality whose efficacy is often limited by poor photosensitizer stability and delivery. In this study, mesoporous silica-coated iron oxide nanoclusters (MNCs) were synthesized and loaded with protoporphyrin IX (PPIX) to obtain a multifunctional PPIX@MNC nanoplatform. Physicochemical characterization was performed using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, and Fourier-transform infrared spectroscopy (FTIR). The biological effects of MNC, free PPIX, and PPIX@MNC were evaluated in HaCaT cells—as a general epithelial model—under dark conditions, light irradiation, cold atmospheric plasma (CAP) exposure, and combined CAP-assisted photodynamic treatment. FTIR, DLS, and zeta potential analyses confirmed successful incorporation of PPIX into the nanoclusters. Cell viability assays revealed pronounced phototoxicity of free PPIX, with the IC50 value decreasing from 44.4 ± 3.5 nM under dark conditions to 14 ± 2 nM following light activation, corresponding to a phototoxicity index of 3.17. CAP further enhanced PPIX-mediated cytotoxicity, and the CAP-assisted photodynamic group exhibited the strongest response, with an IC50 value of 9.6 ± 1.1 nM. CAP further enhanced PPIX-mediated cytotoxicity. Increased ROS generation, enhanced apoptosis, and marked mitochondrial membrane potential disruption were observed particularly in CAP-Light-PPIX-treated cells. Although encapsulation of PPIX within MNCs reduced acute cytotoxicity compared with free PPIX, the nanoplatform retained responsiveness to light and CAP stimulation. These findings demonstrate that CAP potentiates PPIX-mediated photodynamic effects through enhanced oxidative stress and suggest that mesoporous silica-coated magnetic nanoclusters represent a promising platform for controlled photosensitizer delivery in CAP-assisted PDT applications.

Objective: Breast cancer is one of the most frequently diagnosed malignancies in women and a leading cause of cancer-related deaths worldwide. The development of alternative treatment approaches remains a significant area of research. This study aimed to evaluate the cytotoxic effects of CAPE (Capecitabine)-loaded, folate functionalised magnetic mesoporous silica-coated NCs (MS-Fe₃O₄NCs-FA and MS-Fe₃O₄NCs-FA-CAPE), alone and in combination with cold atmospheric plasma (CAP), on the SKBR3 breast cancer cell line.Materials and Methods: MS-Fe₃O₄NCs were synthesised, coated with mesoporous silica, functionalised with folic acid, and loaded with CAPE. SKBR3 cells were treated with MS-Fe₃O₄NCs-FA, MS-Fe₃O₄NCs-FA-CAPE, CAP alone, and combinations thereof. Cell viability and intracellular reactive oxygen species (ROS) levels were examined to assess cytotoxic effects and oxidative stress responses.Results: CAP treatment resulted in decreased cell viability and increased intracellular ROS levels. Co-administration of CAP with CAPE-loaded NCs led to lower IC₅₀ values compared to individual treatments. These findings indicate that CAP may influence cellular responses and nanoparticle-associated cytotoxicity.Conclusion: Co-administration of CAP and folate-functionalised magnetic NCs demonstrated enhanced cytotoxic effects in the SKBR3 cell line. The observed effects may be related to increased oxidative stress and altered membrane properties. Further studies are needed to elucidate the underlying mechanisms and optimise experimental parameters for potential therapeutic applications.