Abstract
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/gFe3o4 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.
Highlights
Pancreatic cancer is the seventh leading cause of cancer deaths [1], being responsible for 6% of all cancer-related deaths
hadron therapy (HT) offers some important advantages in comparison to X-ray radiotherapy: (i) the damage induced on the tumor tissues is generally higher; (ii) as a consequence of point (i), it allows the treatment of radioresistant tumors; (iii) the surrounding healthy cells are kept safe because most energy is deposited within the tumor site (Bragg peak), maximizing the cancer cells damage and (iv) the particle beam remains more collimated along the full path and, any side effects to the adjacent normal tissues can be further reduced [10]
As concerns the combined action of radiotherapy, magnetic nanoparticles (MNPs) and hyperthermia, it should be noted that their effect could be synergistic or additive, as is usual in cancer treatments by means of, e.g., radiotherapy combined with chemotherapy, immunotherapy, surgery, hyperthermia and so on
Summary
Pancreatic cancer is the seventh leading cause of cancer deaths [1], being responsible for 6% of all cancer-related deaths. Datta et al [55] report on two patients with unresectable soft-tissue sarcomas in the lower leg They were treated with local hyperthermia (RF waves) once a week, in combination with a daily proton therapy (for 7 weeks), achieving functional limb preservation with nearly total tumor control. Ahmad et al [57] collected preliminary data on the sensitization of cells to proton therapy using A549 lung cancer cells subjected to hyperthermia treatment (T = 42 ◦C using a heating pad) and to proton irradiation Their results showed that the cell survival fraction dropped on average by 10–15% both at 2 and 4 Gy. As concerns the combined action of radiotherapy, MNPs and hyperthermia, it should be noted that their effect could be synergistic or additive, as is usual in cancer treatments by means of, e.g., radiotherapy combined with chemotherapy, immunotherapy, surgery, hyperthermia and so on. Our experimental results clearly remark the better efficacy of a dual-therapy treatment with respect to single therapy case and pave the way to translate the proposed protocol to clinic
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