Radiation Enhancer Effect of Platinum Nanoparticles in Breast Cancer Cell Lines: In Vitro and In Silico Analyses

Abstract

High-Z metallic nanoparticles (NPs) are new players in the therapeutic arsenal against cancer, especially radioresistant cells. Indeed, the presence of these NPs inside malignant cells is believed to enhance the effect of ionizing radiation by locally increasing the dose deposition. In this context, the potential of platinum nanoparticles (PtNPs) as radiosensitizers was investigated in two breast cancer cell lines, T47D and MDA-MB-231, showing a different radiation sensitivity. PtNPs were internalized in the two cell lines and localized in lysosomes and multivesicular bodies. Analyses of cell responses in terms of clonogenicity, survival, mortality, cell-cycle distribution, oxidative stress, and DNA double-strand breaks did not reveal any significant enhancement effect when cells were pre-exposed to PtNPs before being irradiated, as compared to radiation alone. This result is different from that reported in a previous study performed, under the same conditions, on cervical cancer HeLa cells. This shows that the efficacy of radio-enhancement is strongly cell-type-dependent. Simulation of the early stage ionization processes, taking into account the irradiation characteristics and realistic physical parameters in the biological sample, indicated that PtNPs could weakly increase the dose deposition (by 3%) in the immediate vicinity of the nanoparticles. Some features that are potentially responsible for the biological effect could not be taken into account in the simulation. Thus, chemical and biological effects could explain this discrepancy. For instance, we showed that, in these breast cancer cell lines, PtNPs exhibited ambivalent redox properties, with an antioxidant potential which could counteract the radio-enhancement effect. This work shows that the efficacy of PtNPs for enhancing radiation effects is strongly cell-dependent and that no effect is observed in the case of the breast cancer cell lines T47D and MDA-MB-231. Thus, more extensive experiments using other relevant biological models are needed in order to evaluate such combined strategies, since several clinical trials have already demonstrated the success of combining nanoagents with radiotherapy in the treatment of a range of tumor types.

Antimicrobial Properties of Palladium and Platinum Nanoparticles: A New Tool for Combating Food-Borne Pathogens

“…In this follow-up study, we aimed to examine the potential antimicrobial properties of palladium (PdNPs) and platinum (PtNPs) nanoparticles and their mechanism of action. While PtNPs are believed to induce the intracellular hyper-production of ATP and oxygen radicals, in turn causing bacterial growth inhibition, DNA damage and bacteriotoxic effects [38][39][40], the precise mechanism of action of PdNPs has not been reported to date. Further, we investigated the acute cytotoxicity of NPs on selected cell lines to elucidate the potential impacts of NP exposure on the human population, as there is a gap in the current literature regarding their nanotoxicity [21,22,41].…”

3D Breast Tumor Models for Radiobiology Applications

“…A strong focal point of these 2D studies has been the investigation of ways to enhance radiosensitivity of the cells to overcome radiation resistance. One of the commonly studied methods is the use of metallic nanoparticles [ 54 , 55 , 56 ] and magnetic nanoparticles [ 57 , 58 ] to improve the therapeutic efficiency of radiation treatment of cancer cells. Irradiated nanoparticles enhance the dose deposited locally by producing secondary electrons that add to ROS production and DNA damage within the cell [ 56 ].…”

“…One of the commonly studied methods is the use of metallic nanoparticles [ 54 , 55 , 56 ] and magnetic nanoparticles [ 57 , 58 ] to improve the therapeutic efficiency of radiation treatment of cancer cells. Irradiated nanoparticles enhance the dose deposited locally by producing secondary electrons that add to ROS production and DNA damage within the cell [ 56 ]. Another important strategy has been to repurpose already known small molecule inhibitors and chemotherapeutic drugs to complement irradiation and function as radiosensitizers [ 59 , 60 , 61 , 62 ].…”

The Physical Chemistry and Chemical Physics (PCCP) Section of the International Journal of Molecular Sciences in Its Publications: The First 300 Thematic Articles in the First 3 Years

“…In this Thematic Area, 56 articles have been published [ 48 , 64 , 104 , 108 , 110 , 124 , 195 , 252 , 253 , 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 , 289 , 290 , 291 , 292 , 293 , 294 , 295 , 296 , 297 , 298 , 299 , 300 ], an...…”

“…A more detailed examination shows that, in this direction, as well as in the previous ones, articles in which the objects of research are organic materials clearly prevail over articles in which the objects of research are inorganic materials (36 and 20, respectively). Wherein, the overwhelming majority of articles of the “organic” profile are, in one way or another, connected with the participation of the objects with a biological origin; these include [ 64 , 124 , 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 274 , 277 , 278 , 282 , 284 , 289 , 291 , 292 , 293 , 294 , 295 , 296 , 298 , 299 , 300 ] and the processes in abiogenic organic materials were considered only in [ 48 , 195 , 266 , 271 , 272 , 273 , 283 , 288 , 290 ]. The thematic focus of these works, as well as the chemical compounds studied in them, is also very diverse, and even a simple listing of them here is clearly beyond the scope of this article, too.…”