To overcome chondrosarcoma’s (CHS) high chemo- and radioresistance, we used polyethylene glycol-encapsulated iron oxide nanoparticles (IONPs) for the controlled delivery of the chemotherapeutic doxorubicin (IONP_DOX) to amplify the cytotoxicity of proton radiation therapy. Human 2D CHS SW1353 cells were treated with protons (linear energy transfer (LET): 1.6 and 12.6 keV/µm) with and without IONP_DOX. Cell survival was assayed using a clonogenic test, and genotoxicity was tested through the formation of micronuclei (MN) and γH2AX foci, respectively. Morphology together with spectral fingerprints of nuclei were measured using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module and an axial scanning fluorescence module, as well as scanning electron microscopy (SEM) coupled with energy-dispersive X-Ray spectroscopy (EDX). Cell survival was also determined in 3D SW3153 spheroids following treatment with low-LET protons with/without the IONP_DOX compound. IONP_DOX increased radiosensitivity following proton irradiation at both LETs in correlation with DNA damage expressed as MN or γH2AX. The IONP_DOX–low-LET proton combination caused a more lethal effect compared to IONP_DOX–high-LET protons. CHS cell biological alterations were reflected by the modifications in the hyperspectral images and spectral profiles, emphasizing new possible spectroscopic markers of cancer therapy effects. Our findings show that the proposed treatment combination has the potential to improve the management of CHS.

Flash irradiation is an innovative method of therapy, which ensures that the therapeutic dose is brought to the pathological focus in times of the order of several tens of milliseconds. In this mode of irradiation, the degree of damage to normal tissues surrounding the tumor that fall under the influence of radiation decreases; at the same time, the effect on cancer cells remains at almost the same level, which improves the prospect of local control of the tumor with a lower frequency of side effects. The exact radiobiological mechanisms underlying the flash effect are not completely clear. This paper presents the results of work on the formation of a high-intensity proton beam with an energy of 660 MeV from the phasotron accelerator of the Joint Institute for Nuclear Research (Dubna), designed to conduct radiobiological studies of flash irradiation therapy on cell cultures and small laboratory animals (mice and rats). The survival rate of A549 cells under proton beam irradiation in flash and standard modes was compared. A difference was found in the change in the survival rate of A549 cells irradiated in flash and standard modes. The magnitude of the flash effect was represented by the dose change factor.

FLASH radiotherapy is the innovative radiotherapy technique in which the short treatment times, few tens of milliseconds, are used to deliver a therapeutic dose of radiation to the tumor. This novel approach reduces damage and minimizes the dose to normal tissues surrounding the tumor and to tissues that are affected by radiation, whilst maintaining the treatment effect on cancer cells. This regimen may improve the level of local control of the tumor and lower the occurrence of side effects. To date, the exact radiobiological mechanisms underpinning the FLASH effect are not completely understood. The paper presents the results on the delivery of a high-intensity proton beam at an energy of 660 MeV produced by Phasotron, a proton accelerator at the Joint Institute for Nuclear Research, Dubna. This proton beam has been created to perform radiobiological studies involving cell cultures and small laboratory animals (mice, rats) using FLASH radiation. Also, the survival rates were compared between A549 cells irradiated at extremely high dose rates (FLASH technique) and those exposed to conventional irradiation with the lower dose rate. It was found that there is a difference between these groups of A549 cells in the survival rates. The magnitude of the FLASH effect is represented by a factor of different dose rates.