Penetration and intracellular uptake of poly(glycerol-adipate)nanoparticles into 3-dimensional brain tumour cell culture models

Nanoparticle (NP) drug delivery systems may potentially enhance the efficacy of therapeutic agents. It is difficult to characterise many important properties of NPs in vivo and therefore attempts have been made to use realistic in vitro multicellular spheroids instead. In this paper we have evaluated poly(glycerol-adipate) (PGA) NPs as a potential drug carrier for local brain cancer therapy. Various 3-dimensional (3-D) cell culture models have been used to investigate the delivery properties of PGA NPs. Tumour cells in 3-D culture showed a much higher level of endocytic uptake of NPs than a mixed normal neonatal brain cell population. Differences in endocytic uptake of NPs in 2-D and 3-D models strongly suggest that it is very important to use in vitro 3-D cell culture models for evaluating this parameter. Tumour penetration of NPs is another important parameter which could be studied in 3-D cell models. The penetration of PGA NPs through 3-D cell culture varied between models, which will therefore require further study to develop useful and realistic in vitro models. Further use of 3-D cell culture models will be of benefit in the future development of new drug delivery systems, particularly for brain cancers which are more difficult to study in vivo

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

Gold nanoparticle (GNP) boosted radiation therapy can enhance the biological effectiveness of radiation treatments by increasing the quantity of direct and indirect radiation-induced cellular damage. As the physical effects of GNP boosted radiotherapy occur across energy scales that descend down to 10 eV, Monte Carlo simulations require discrete physics models down to these very low energies in order to avoid underestimating the absorbed dose and secondary particle generation. Discrete physics models for electron transportation down to 10 eV have been implemented within the Geant4-DNA low energy extension of Geant4. Such models allow the investigation of GNP effects at the nanoscale. At low energies, the new models have better agreement with experimental data on the backscattering coefficient, and they show similar performance for transmission coefficient data as the Livermore and Penelope models already implemented in Geant4. These new models are applicable in simulations focussed towards estimating the relative biological effectiveness of radiation in GNP boosted radiotherapy applications with photon and electron radiation sources

Cosmic-Ray Tracks in Astrophysical Ices: Modeling with the Geant4-DNA Monte Carlo Toolkit

Cosmic rays are ubiquitous in interstellar environments, and their bombardment of dust-grain ice mantles is a possible driver for the formation of complex, even prebiotic molecules. Yet, critical data that are essential for accurate modeling of this phenomenon, such as the average radii of cosmic-ray tracks in amorphous solid water (ASW) remain unconstrained. It is shown that cosmic-ray tracks in ASW can be approximated as a cylindrical volume with an average radius that is mostly independent of the initial particle energy. Interactions between energetic ions and both low-density amorphous (LDA) and high-density amorphous (HDA) ice targets are simulated using the Geant4-DNA Monte Carlo toolkit, which allows for tracking secondary electrons down to subexcitation energies in the material. We find the peak track-core radii, r cyl, for LDA and HDA ices to be 9.9 nm and 8.4 nm, respectively-somewhat less than double the value of 5 nm often assumed in astrochemical models. © 2020. The American Astronomical Society. All rights reserved

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

Gold nanoparticle (GNP) boosted radiation therapy can enhance the biological effectiveness of radiation treatments by increasing the quantity of direct and indirect radiation-induced cellular damage. As the physical effects of GNP boosted radiotherapy occur across energy scales that descend down to 10 eV, Monte Carlo simulations require discrete physics models down to these very low energies in order to avoid underestimating the absorbed dose and secondary particle generation. Discrete physics models for electron transportation down to 10 eV have been implemented within the Geant4-DNA low energy extension of Geant4. Such models allow the investigation of GNP effects at the nanoscale. At low energies, the new models have better agreement with experimental data on the backscattering coefficient, and they show similar performance for transmission coefficient data as the Livermore and Penelope models already implemented in Geant4. These new models are applicable in simulations focussed towards estimating the relative biological effectiveness of radiation in GNP boosted radiotherapy applications with photon and electron radiation sources

Calculated electronic energy loss of swift proton and helium ion beams in liquid water

Paper submitted to the 9th International Conference on Applications of Nuclear Techniques, Crete, Greece, 8–14 June 2008.The electronic energy loss of swift proton and helium beams in liquid water is theoretically evaluated. Our model is based in the dielectric formalism, taking into account the charge exchange of the projectile during its travel through the target. The electronic properties of liquid water are described by the MELF-GOS model, where the outer electron excitations are represented by a sum of Mermin functions fitted to the experimental data in the optical limit, whereas the inner-shell electron excitations are modelled by the corresponding atomic generalized oscillator strength. The inverse mean free path, the stopping power and the energy loss straggling are calculated, showing a reasonably good agreement with the available experimental data.This work has been financially supported by the Spanish Ministerio de Educación y Ciencia (Contract Nos. FIS2006-13309-C02-01 and FIS2006-13309-C02-02). C.D.D. thanks the Spanish Ministerio de Educación y Ciencia for support under the Ramón y Cajal Program

An analytic dosimetry study for the use of radionuclide liposome conjugates in internal radiotherapy

A dosimetric analysis has been performed to evaluate the po-tential of liposome systems as carriers of radionuclides in inter-nal radiotherapy. Methods: Pharmacokinetic data for a variety of liposome constructs (multilamellar vesicles [MLV]; small unilamellar vesicles [SUV]; and sterically stabilized liposomes, monosialoganglioside [GM1]-coated) were used to obtain tumor and normal-organ absorbed dose estimates for 67Cu, 188Re, 90Y, and 131I. Dosimetry was performed for two tumor models: sub-cutaneous Ehrlich ascites tumor, growing intramuscularly, and C26 colon carcinoma, growing intrahepatically. Dose estimates were obtained using the MIRD schema. Tumor doses were obtained assuming local deposition of electron energy; photon contributions were incorporated assuming spheric tumor geom-etry. With the conservative assumption that intravenously ad-ministered liposomes achieve rapid equilibration with the re