This study aimed to develop and compare single and multiple 3D models such as multicellular tumor spheroids and to investigate the influence of Matrigel on their morphological and functional behavior. MDA-MB-231 3D models were generated in the presence and absence of Matrigel and their key biological properties within 6 days of culture were monitored. Our results revealed the formation of well-defined 3D models in the presence of Matrigel, with a uniform morphology, increased diameter, good circularity, and increased expression of a proliferation marker (PCNA). In comparison, 3D models generated without Matrigel were characterized by an irregular border, reduced dimensions and circularity, and a decrease of PCNA expression. Similarities between the single and multiple 3D cultures were found in their viability, Nrf2 expression, and glutathione (GSH) content. The influence of Matrigel on MDA-MB-231 spheroids metabolism under hypoxic conditions was highlighted by released lactate dehydrogenase and nitric oxide, GSH levels and expression of Nrf2 and Hsp70 proteins. Based on the increased expression of PCNA and the development of the hypoxia process in the presence of extracellular matrix, our study showed that the addition of Matrigel improves the growing environment of tumor spheroids, making it closer to that of in vivo tumor conditions.

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In this paper we developed a method for multiwalled carbon nanotubes (MWCNTs) use as carriers for a drug based on platinum in breast cancer therapy. The method of functionalization involves the carboxyl functionalization of nanotubes and encapsulation of cisplatin (CDDP) into MWCNTs. The biological properties of MWCNTs loaded with CDDP (MWCNT-COOH-CDDP) and of individual components MWCNT-COOH and free CDDP were evaluated on MDA-MB-231 cells. Various concentrations of CDDP (0.316–2.52 µg/mL) and MWCNTs (0.5–4 µg/mL) were applied on cells for 24 and 48 h. Only at high doses of CDDP (1.26 and 2.52 µg/mL) and MWCNT-COOH-CDDP (2 and 4 µg/mL) cell morphological changes were observed. The cellular viability decreased only with approx. 40% after 48 h of exposure to 2.52 µg/mL CDDP and 4 µg/mL MWCNT-COOH-CDDP despite the high reactive oxygen species (ROS) production induced by MWCNTs starting with 24 h. After 48 h, ROS level dropped as a result of the antioxidant defence activation. We also found a significant decrease of caspase-3 and p53 expression after 48 h, accompanied by a down-regulation of NF-κB in cells exposed to MWCNT-COOH-CDDP system which promotes apoptosis escape and thus failing to overcome the triple negative breast cancer (TNBC) cells resistance.

The purpose of this study was to investigate the effectiveness in photodynamic therapy of iron oxide nanoparticles (γ-Fe2O3 NPs), synthesized by laser pyrolysis technique, functionalized with 5,10,15,20-(Tetra-4-sulfonatophenyl) porphyrin tetraammonium (TPPS) on human cutaneous melanoma cells, after only 1 min blue light exposure. The efficiency of porphyrin loading on the iron oxide nanocarriers was estimated by using absorption and FTIR spectroscopy. The singlet oxygen yield was determined via transient characteristics of singlet oxygen phosphorescence at 1270 nm both for porphyrin functionalized nanoparticles and rose bengal used as standard. The irradiation was performed with a LED (405 nm, 1 mW/cm2) for 1 min after melanoma cells were treated with TPPS functionalized iron oxide nanoparticles (γ-Fe2O3 NPs_TPPS) and incubated for 24 h. Biological tests revealed a high anticancer effect of γ-Fe2O3 NPs_TPPS complexes indi-cated by the inhibition of tumor cell proliferation, reduction of cell adhesion, and induction of cell death through ROS generated by TPPS under light exposure. The biological assays were combined with the pharmacokinetic prediction of the porphyrin.

PI3K/Akt signaling is one of the most frequently dysregulated pathways in cancer, including triple-negative breast cancer. With considerable roles in tumor growth and proliferation, this pathway is studied as one of the main targets in controlling the therapies’ efficiency. Nowadays, the development of nanoparticle–drug conjugates attracts a great deal of attention due to the advantages they provide in cancer treatment. Hence, the main purpose of this study was to design a nanoconjugate based on single-walled carbon nanotubes functionalized with carboxyl groups (SWCNT-COOH) and cisplatin (CDDP) and to explore the potential of inhibiting the PI3K/Akt signaling pathway. MDA-MB-231 cells were exposed to various doses (0.01–2 µg/mL SWCNT-COOH and 0.00632–1.26 µg/mL CDDP) of SWCNT-COOH-CDDP and free components for 24 and 48 h. In vitro biological tests revealed that SWCNT-COOH-CDDP had a high cytotoxic effect, as shown by a time-dependent decrease in cell viability and the presence of a significant number of dead cells in MDA-MB-231 cultures at higher doses. Moreover, the nanoconjugates induced the downregulation of PI3K/Akt signaling, as revealed by the decreased expression of PI3K and p-Akt in parallel with PTEN activation, the promotion of Akt protein degradation, and inhibition of tumor cell migration.