Using rare-earth based nanoscintillators for X-ray induced photodynamic therapy
Bibliographic record
Abstract
Pancreatic cancer is associated with a poor prognosis despite multimodal treatments consisting in surgery, chemotherapy and radiotherapy . Photodynamic therapy (PDT) is a promising treatment that aims to activate photosensitizers with light in order to induce local cell damage. However, its use for treating deep tumors, including pancreatic tumors , is limited because of the low penetration depth of light in tissues. To overcome this limitation, it has been proposed to use nanoscintillators (NS) that down-convert ionizing radiation such as X-rays used in radiotherapy , into UV-visible photons. These nanoparticles could improve the efficacy of radiotherapy through at least three effects: the radiation dose-enhancement effect 1 that is a physical effect due to the accumulation of heavy elements in the vicinity of tumors, the emission of UV-C photons that increase direct DNA damage, and the activation of photodynamic therapy by X-rays (X-PDT) 2 . The aim of our project is to conjugate NS with appropriate photosensitizers to achieve PDT during radiotherapy. Here, we present our results obtained with lanthanum fluoride nanoscintillators doped with cerium (LaF 3 :Ce) coated with either triphosphate or polyethylene glycol (PEG). The choice of the coating is of major importance because it could modify the NS toxicity and uptake in cells and microtumors, and thus impact their therapeutic efficacy. We studied the properties of NS on both 2D and 3D culture models of pancreatic tumors , grown in suspension or as adherent microtumors. As LaF 3 :Ce nanoparticles are only excited by UV photons, they could not be observed with a conventional confocal microscope . Therefore, we used X-ray fluorescence microscopy (ID16, ESRF) and transmission electron microscopy (IBS) to analyze their distribution within the cells, and X-ray fluorescence microtomography (P06, DESY) to study their accumulation in tumor spheroids. We observed that NS functionalized with triphosphate coating formed many aggregates and were present in greater amounts within the cells, compared to those with PEG coating. These experiments also showed a higher concentration of lanthanum – the main constituent of NS – inside the tumor spheroids when a triphosphate coating was used. We obtained similar intrinsic toxicities for both coatings, and promising preliminary results regarding the therapeutic potential of LaF 3 :Ce NS. We are currently investigating the role of the NS coating on treatment efficacy, biodistribution and pharmacokinetics using in vivo models of pancreatic tumors. Finally, their conjugation with photosensitizers will be investigated to evaluate X-PDT efficacy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".