Biology subjects

Bayart, E.

Publications and source records attributed to Bayart, E..

3 recordsLinked to original sources

bioRxiv2025

Laser-driven VHEE pulsed fast fractionation (PFF): second-scale inter-pulse timing differentially modulates normal tissue and tumour toxicity

Radiotherapy (RT) is constrained by the narrow therapeutic window between tumour control and normal-tissue toxicity. While FLASH RT has been reported to reduce normal-tissue toxicity at ultra-high dose rates (UHDR) while preserving tumour control in several preclinical models, the radiobiological potential of intermediate temporal regimes between conventional fractionation and FLASH remains largely unexplored. Here, we show that temporal separation of ultrashort (fs-ps) dose-delivery pulses delivered at ultra-high instantaneous dose rate, with second-scale inter-pulse intervals, can differentially modulate biological response in vitro and in vivo. Samples were irradiated with very high-energy electrons (VHEEs, 50 MeV to 300 MeV) generated by a laser-plasma accelerator (LPA), using a temporal irradiation modality we term pulsed fast fractionation (PFF), with instantaneous dose rates exceeding 10^12 Gy/s. Varying the inter-pulse interval from 1 s to 10 s while maintaining dose per pulse and total dose constant modulated biological response in both in vitro and in vivo models. At the shortest investigated inter-pulse interval ({theta} = 1s), MRC5-hTERT human fibroblasts showed higher viability, whereas HCT116 colorectal carcinoma cells showed lower viability under matched dose conditions. In vivo, the same interval was associated with reduced radiation-induced growth impairment in zebrafish embryos, consistent with the response pattern observed in the non-tumour cell model and extending this timing-dependent response to a whole-organism context. These findings identify second-scale pulse timing as a biologically active degree of freedom for VHEE delivery, positioning PFF as a distinct temporal irradiation regime with the potential to complement spatial dose modulation through temporal optimisation and extend the current fractionation-FLASH framework.

cell biology↗

bioRxiv2025

Comparative analysis of the radiobiological effects of laser-driven VHEE vs. conventional electrons using in vitro, ex vivo, and in vivo models

PurposeThis study systematically investigates the radiobiological effects of Very High Energy Electrons (VHEE) generated by a laser-plasma accelerator (LPA), in comparison with Conventional Intermediate Energy Electrons (CIEE) from a conventional linear accelerator (LINAC). Using in vitro, ex vivo, and in vivo models, we evaluate and compare their potential toxicity on healthy tissues. Methods and MaterialsCell survival, tissue response, and developmental toxicity were assessed across three biological models. In vitro, human fibroblasts (MRC5-hTERT) were used to generate post-irradiation survival curves. Ex vivo, precision-cut lung slices (PCLS) from mice were analyzed for radiation-induced inhibition of cell proliferation. In vivo, zebrafish embryos were used to evaluate developmental toxicity through body length and spinal curvature measurements. VHEE irradiations were performed using a broadband electron beam spanning 50-300 MeV, using the Salle Jaune LPA (Laboratoire dOptique Appliquee, France), while CIEE exposures were performed with a 7 MeV conventional LINAC (Institut Curie, France). ResultsIn vitro, MRC5-hTERT cells showed no significant difference in radiosensitivity between VHEE and CIEE, with comparable D10 values (p-value = 0.7). In the ex vivo model, both beams induced a dose-dependent decrease in cell division with no significant inter-beam differences at any dose level (p-value > 0.99). In vivo, zebrafish embryos exhibited dose-dependent body shortening and increased spinal curvature following both VHEE and CIEE exposure. No significant differences were observed between the two modalities at matched doses for any measured metric (p-value[≥] 0.5). ConclusionThis study presents the first comprehensive radiobiological evaluation of a laser-driven VHEE beam across multiple biological models. Under the investigated conditions, VHEE and CIEE irradiations exhibit similar biological toxicity. These findings support the feasibility and potential of VHEE generated with LPA for future clinical applications.

cell biology↗

bioRxiv2019

Fast dose fractionation using ultra-short laser accelerated proton pulses can increase cancer cell mortality, which relies on functional PARP1 protein

Radiotherapy is a cornerstone of cancer management. The improvement of spatial dose distribution in the tumor volume by minimizing the dose deposited in the healthy tissues have been a major concern during the last decades. Temporal aspects of dose deposition are yet to be investigated. Laser-plasma-based particle accelerators are able to emit pulsed-proton beams at extremely high peak dose rates (~109 Gy/s) during several nanoseconds. The impact of such dose rates on resistant glioblastoma cell lines, SF763 and U87-MG, was compared to conventionally accelerated protons and X-rays. No difference was observed in DNA double-strand breaks generation and cells killing. The variation of the repetition rate of the proton bunches produced an oscillation of the radio-induced cell susceptibility in HCT116 cells, which appeared to be related to the presence of the PARP1 protein and an efficient parylation process. Interestingly, when laser-driven proton bunches were applied at 0.5 Hz, survival of the radioresistant HCT116 p53-/- cells equaled that of its radiosensitive counterpart, HCT116 WT, which was also similar to cells treated with the PARP1 inhibitor Olaparib. Altogether, these results suggest that the application modality of ultrashort bunches of particles could provide a great therapeutic potential in radiotherapy.

cancer biology↗