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.

In this study, we report the realization of drug-loaded smart magnetic nanocarriers constituted by superparamagnetic iron oxide nanoparticles encapsulated in a dual pH- and temperature-responsive poly (N-vinylcaprolactam-co-acrylic acid) copolymer to achieve highly controlled drug release and localized magnetic hyperthermia. The magnetic core was constituted by flower-like magnetite nanoparticles with a size of 16.4 nm prepared by the polyol approach, with good saturation magnetization and a high specific absorption rate. The core was encapsulated in poly (N-vinylcaprolactam-co-acrylic acid) obtaining magnetic nanocarriers that revealed reversible hydration/dehydration transition at the acidic condition and/or at temperatures above physiological body temperature, which can be triggered by magnetic hyperthermia. The efficacy of the system was proved by loading doxorubicin with very high encapsulation efficiency (>96.0%) at neutral pH. The double pH- and temperature-responsive nature of the magnetic nanocarriers facilitated a burst, almost complete release of the drug at acidic pH under hyperthermia conditions, while a negligible amount of doxorubicin was released at physiological body temperature at neutral pH, confirming that in addition to pH variation, drug release can be improved by hyperthermia treatment. These results suggest this multi-stimuli-sensitive nanoplatform is a promising candidate for remote-controlled drug release in combination with magnetic hyperthermia for cancer treatment.

Heterodimeric nanoparticles comprising materials with different functionalities are of great interest for fundamental research and biomedical/industrial applications. In this work, Fe₃O₄-Au nano-heterostructures were synthesized by a one-step thermal decomposition method. The hybrid nanoparticles comprise a highly crystalline 12 nm magnetite octahedron decorated with a single noble metal sphere of 6 nm diameter. Detailed analysis of the nanoparticles was performed by UV-visible spectroscopy, magnetometry, calorimetry and relaxometry studies. The cytotoxic effect of the nanoparticles in the human hepatic cell line Huh7 and PLC/PRF/5-Alexander was also assessed. These Fe₃O₄-Au bifunctional nanoparticles showed no significant cytotoxicity in these two cell lines. The nanoparticles showed a good theranostic potential for liver cancer treatment, since the r₂ relaxivity (166.5 mM⁻¹·s⁻¹ and 99.5 mM⁻¹·s⁻¹ in water and HepG2 cells, respectively) is higher than the corresponding values for commercial T₂ contrast agents and the Specific Absorption Rate (SAR) value obtained (227 W/g_Fe) is enough to make them suitable as heat mediators for Magnetic Fluid Hyperthermia. The gold counterpart can further allow the conjugation with different biomolecules and the optical sensing.