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To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down‐convert X‐rays into photons with energies ranging from UV to near‐infrared. During radiotherapy, these scintillating properties amplify radiation‐induced damage by UV‐C emission or photodynamic effects. Additionally, nanoscintillators that contain high‐Z elements are likely to induce another, currently unexplored effect: radiation dose‐enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X‐rays by high‐Z elements compared to tissues, resulting in increased production of tissue‐damaging photo‐ and Auger electrons. In this study, Geant4 simulations reveal that rare‐earth composite LaF3:Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF3:Ce highly concentrates in microtumors and enhances radiotherapy in an X‐ray energy‐dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF3:Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose‐enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers. Radiation dose‐enhancement induced by rare‐earth composite nanoscintillators is predicted by in silico simulations and unequivocally demonstrates in vitro in microtumor models of glioblastoma, using tunable monochromatic synchrotron radiation. Radiation dose‐enhancement ultimately elicitsa prominent radiotherapeutic effect in a syngeneic orthotopic model of aggressive glioblastoma. These results prove the strong ability of rare‐earth composite nanoscintillators to enhance the focal damage of radiotherapy.

Pancreatic cancer is associated with a poor prognosis despite multimodal treatments. To improve the efficacy of radiotherapy, the use of nanoscintillators is emerging. Made of high‐Z elements, they absorb X‐rays more efficiently than tissues and can locally enhance the radiation dose provided they have accumulated near tumor cells. This study focuses on the role of the coating, a key parameter that controls both in vitro and in vivo properties of nanoparticles, including their internalization, biocompatibility, and therapeutic efficacy. Polyethylene glycol and tripolyphosphate molecules are used to coat lanthanum fluoride nanoscintillators, and their properties are evaluated on pancreatic cancer models. The experiments demonstrate a higher internalization of the nanoparticles when coated with tripolyphosphate, in both 2D and 3D culture models, correlating with greater efficacy under X‐rays, which may be associated with higher radiation dose‐enhancement. The nanoparticles are also injected intravenously in healthy or tumor‐bearing mice in order to study their toxicity, pharmacokinetics, and biodistribution. Despite a strong liver and spleen accumulation, especially for the tripolyphosphate‐coated nanoparticles, no toxicity is observed for either coating. Because they show promising radiation dose‐enhancement in vitro in both culture models and a limited toxicity in vivo, polyethylene glycol‐coated nanoparticles are good candidates for biomedical applications.

In nanoparticle (NP)-enhanced orthovoltage radiotherapy, bone scatter affected dose enhancement at the skin lesion in areas such as the forehead, chest wall, and knee. Since each of these treatment sites have a bone, such as the frontal bone, rib, or patella, underneath the skin lesion and this bone is not considered in dose delivery calculations, uncertainty arises in the evaluation of dose enhancement with the addition of NPs in radiotherapy. To investigate the impact of neglecting the effect of bone scatter, Monte Carlo simulations based on heterogeneous phantoms were carried out to determine and compare the dose enhancement ratio (DER), when a bone was and was not present underneath the skin lesion. For skin lesions with added NPs, Monte Carlo simulations were used to calculate the DER values using different elemental NPs (gold, platinum, silver, iodine, as well as iron oxide), in varying NP concentrations (3–40 mg/mL), at two different photon beam energies (105 and 220 kVp). It was found that DER values at the skin lesion increased with the presence of bone when there was a higher atomic number of NPs, a higher NP concentration, and a lower photon beam energy. When comparing DER values with and without bone, using the same NP elements, NP concentration, and beam energy, differences were found in the range 0.04–3.55%, and a higher difference was found when the NP concentration increased. By considering the uncertainty in the DER calculation, the effect of bone scatter became significant to the dose enhancement (>2%) when the NP concentration was higher than 18 mg/mL. This resulted in an underestimation of dose enhancement at the skin lesion, when the bone underneath the tumour was neglected during orthovoltage radiotherapy.

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.

To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas. Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays. Gold uptake gave a 19:1 tumor to normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died. Intravenously injected gold nanoparticles cross the blood-tumor barrier, but are largely blocked by the normal blood-brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers. Original submitted 14 February 2012; Revised submitted 16 September 2012; Published online 24 December 2012

While gold nanoparticles (GNP)s in proton therapy are widely assumed to exert radio-sensitization via mechanism of secondary electron emission, the discrepancies between simulations and experimental outcomes shows that, in some cases, the secondary electron hypothesis fails to explain the experimental observations particularly distant DNA damage beyond the range of low-energy electrons. These persistent discrepancies show weaknesses of this mechanism, as noted by multiple studies. Resolving the long-standing discrepancy is the main purpose of present research. We predict the survival fractions and sensitization enhancement by Geant4 to bridge the gap between simulation and in-vitro data. Through Geant4 Monte Carlo simulations we demonstrate that proton stopping – not electron emission- by GNPs is the dominant mechanism, driving the GNP enhanced proton therapy via amplification of proton’s linear energy transfer (LET). For the first time, our model successfully reconciles simulation with experimental data by quantifying the key radiobiological parameters: dose enhancement ratio (DER) and sensitization enhancement ratio (SER). These findings redefine GNPs as proton energy modulators rather than electron emitters, resolving the long-standing simulation-experiment discrepancies. However, it is emphasized that, the secondary electron emission from metallic NPs in the range of nano-scale have remarkable impact. Furthermore, we derive a mathematical relationship between DER and cell survival fraction (SF) in the linear-quadratic (LQ) model with predicted survival curves showing strong agreement with in-vitro data.

Nanoparticles (NPs) with a high atomic number (Z) are promising radiosensitizers for cancer therapy. However, the dependence of their efficacy on irradiation conditions is still unclear. In the present work, 11 different metal and metal oxide NPs (from Cu (ZCu = 29) to Bi2O3 (ZBi = 83)) were studied in terms of their ability to enhance the absorbed dose in combination with 237 X-ray spectra generated at a 30–300 kVp voltage using various filtration systems and anode materials. Among the studied high-Z NP materials, gold was the absolute leader by a dose enhancement factor (DEF; up to 2.51), while HfO2 and Ta2O5 were the most versatile because of the largest high-DEF region in coordinates U (voltage) and Eeff (effective energy). Several impacts of the X-ray spectral composition have been noted, as follows: (1) there are radiation sources that correspond to extremely low DEFs for all of the studied NPs, (2) NPs with a lower Z in some cases can equal or overcome by the DEF value the high-Z NPs, and (3) the change in the X-ray spectrum caused by a beam passing through the matter can significantly affect the DEF. All of these findings indicate the important role of carefully planning radiation exposure in the presence of high-Z NPs.

Nanomaterials have garnered significant attention due to their unique properties and wide-ranging applications in medicine and biophysics. However, their interactions with biological systems, particularly DNA, raise critical concerns about genotoxicity and potential long-term health risks. This review delves into the biophysical mechanisms underlying nanomaterial-induced DNA damage, highlighting recent insights, current challenges, and future research directions. We explore how the physicochemical properties of nanomaterials influence their interaction with DNA, the pathways through which they induce damage, and the biophysical methods employed to study these processes.

The development of theranostic nanostructures is one of the most advanced branches of pharmaceutical and medical sciences in the world today. Due to the unique properties such as surface plasmon resonance, Raman signal amplification, high atomic number, gold nanostructures are of particular interest to researchers. It has been shown that the formation of mesoporous silica coating with suitable thickness and microstructural properties can increase thermal stability and increase the possibility of loading anticancer drugs in theranostic formulations. In this study, gold nanorods were synthesized by seed-mediated growth method, and then by the sol-gel technique, nanorods were used as a template to create mesoporous silica coating. In the last step, PEG silane was used to create a polyethylene glycol coating at the surface of nanostructures. Based on HRTEM micrographs, the fabricated nanostructures had an average size of approximately 80 nm, and the nanoparticles entirely separated from each other. These nanostructures were non-toxic and could be well used as X-ray contrast agents. Only at high concentrations, these nanostructures were able to have a significant effect on radiotherapy with cobalt 60 source.

The recent progress in Nanotechnology has introduced Gold Nanoparticles (AuNPs) as promising radiosensitizing agents in radiation oncology. This work aims to estimate dose enhancement due to the presence of AuNPs inside an irradiated water region through Monte Carlo calculations. The GATE platform was used to simulate 6 MV photon histories generated from a TrueBeam® linear accelerator with and without a Flattening Filter (FF) and model AuNPs clusters. The AuNPs size, concentration and distribution pattern were examined. To investigate different clinical irradiation conditions, the effect of field size, presence of FF and placement of AuNPs in water were evaluated. The range of Dose Enhancement Factors (DEF = DoseAu/DoseWater) calculated in this study is 0.99 ± 0.01–1.26 ± 0.02 depending on photon beam quality, distance from AuNPs surface, AuNPs size and concentration and pattern of distribution. The highest DEF is reported for irradiation using un-flattened photon beams and at close distances from AuNPs. The obtained findings suggest that dose deposition could be increased in regions that represent whole cells or subcellular targets (mitochondria, cell nucleus, etc.). Nevertheless, further and consistent research is needed in order to make a step toward AuNP-aided radiotherapy in clinical practice.