A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0–2 Gy for carbon ions and 0–7 Gy for 6 MV photons. Hyperthermia is realized via a standard heating bath, assisted by magnetic fluid hyperthermia (MFH) that utilizes magnetic nanoparticles (MNPs) exposed to an alternating magnetic field of amplitude 19.5 mTesla and frequency 109.8 kHz. Starting from 37 °C, the temperature is gradually increased and the sample is kept at 42 °C for 30 min. For MFH, MNPs with a mean diameter of 19 nm and specific absorption rate of 110 ± 30 W/g_Fe3o₄ coated with a biocompatible ligand to ensure stability in physiological media are used. Irradiation diminishes the clonogenic survival at an extent that depends on the radiation type, and its decrease is amplified both by the MNPs cellular uptake and the hyperthermia protocol. Significant increases in DNA double-strand breaks at 6 h are observed in samples exposed to MNP uptake, treated with 0.75 Gy carbon-ion irradiation and hyperthermia. The proposed experimental protocol, based on the combination of hadron irradiation and hyperthermia, represents a first step towards an innovative clinical option for pancreatic cancer.

Background: TiO₂ nanoparticles (TiO₂ NPs) are the nanomaterial most produced as an ultraviolet (UV) filter. However, TiO₂ is a semiconductor and, in nanoparticle size, is a strong photocatalyst, raising concerns about photomutagenesis. Mesoporous silica nanoparticles (MSN) were synthetized incorporating TiO₂ NPs (TiO₂@MSN) to develop a cosmetic UV filter. The aim of this study was to assess the toxicity of TiO₂@MSN, compared with bare MSN and commercial TiO₂ NPs, based on several biomarkers. Materials and Methods: Human peripheral blood mononuclear cells (PBMC) were exposed to TiO₂@MSN, bare MSN (network) or commercial TiO₂ NPs for comparison. Exposed PBMC were characterized for cell viability/apoptosis, reactive oxygen species (ROS), nuclear morphology, and cytokines secretion. Results: All the nanoparticles induced apoptosis, but only TiO₂ NPs (alone or assembled into MSN) led to ROS and micronuclei. However, TiO₂@MSN showed lower ROS and cytotoxicity with respect to the P25. Exposure to TiO₂@MSN induced Th2-skewed and pro-fibrotic responses. Conclusions: Geno-cytotoxicity data indicate that TiO₂@MSN are safer than P25 and MSN. Cytokine responses induced by TiO₂@MSN are imputable to both the TiO₂ NPs and MSN, and, therefore, considered of low immunotoxicological relevance. This analytical assessment might provide hints for NPs modification and deep purification to reduce the risk of health effects in the settings of their large-scale manufacturing and everyday usage by consumers.