Małgorzata A. Śmiałek

Gold nanoparticles for cancer radiotherapy: a review

Radiotherapy is currently used in around 50% of cancer treatments and relies on the deposition of energy directly into tumour tissue. Although it is generally effective, some of the deposited energy can adversely affect healthy tissue outside the tumour volume, especially in the case of photon radiation (gamma and X-rays). Improved radiotherapy outcomes can be achieved by employing ion beams due to the characteristic energy deposition curve which culminates in a localised, high radiation dose (in form of a Bragg peak). In addition to ion radiotherapy, novel sensitisers, such as nanoparticles, have shown to locally increase the damaging effect of both photon and ion radiation, when both are applied to the tumour area. Amongst the available nanoparticle systems, gold nanoparticles have become particularly popular due to several advantages: biocompatibility, well-established methods for synthesis in a wide range of sizes, and the possibility of coating of their surface with a large number of different molecules to provide partial control of, for example, surface charge or interaction with serum proteins. This gives a full range of options for design parameter combinations, in which the optimal choice is not always clear, partially due to a lack of understanding of many processes that take place upon irradiation of such complicated systems. In this review, we summarise the mechanisms of action of radiation therapy with photons and ions in the presence and absence of nanoparticles, as well as the influence of some of the core and coating design parameters of nanoparticles on their radiosensitisation capabilities.

Quantification of Radiation-Induced Single-Strand Breaks in Plasmid DNA using a TUNEL/ELISA-Based Assay

Abstract To accurately quantify the number of single-strand breaks (SSBs) induced in plasmid DNA molecules after irradiation, a new type of assay methodology has been explored. The new method is based on the TUNEL (terminal deoxynucleotide transferase dUTP nick end-labeling) assay that was adopted for use under ELISA (enzyme-linked immunosorbent assay) conditions. The assay was found to both improve the quantification and reduce the uncertainties in measurement of SSBs compared with the commonly used agarose gel electrophoresis (AGE) method. Together with AGE, the new method can provide the additional data necessary for an accurate analysis of both SSB and double-strand break (DSB) formation in DNA molecules after irradiation. Furthermore, since only small amounts of DNA are required, the ELISA method can be used to quantify the damage in samples of DNA that are smaller than those required for AGE analysis. As an example of the data obtainable using the new method, plasmid DNA samples were irradiated with vacuum-ultraviolet (VUV) light in an aqueous solution at 170 nm and subsequently analyzed by ELISA. The results were compared directly with those from AGE analysis. The ELISA gave results for SSBs that were an order of magnitude higher than those from AGE and suggested that DSBs are more likely to be the result of two SSBs rather than a single event and that a damaged molecule is more likely to be susceptible to VUV light than an undamaged one.

Valence and ionic lowest-lying electronic states of ethyl formate as studied by high-resolution vacuum ultraviolet photoabsorption, He(I) photoelectron spectroscopy, and ab initio calculations

The highest resolution vacuum ultraviolet photoabsorption spectrum of ethyl formate, C2H5OCHO, yet reported is presented over the wavelength range 115.0-275.5 nm (10.75-4.5 eV) revealing several new spectral features. Valence and Rydberg transitions and their associated vibronic series, observed in the photoabsorption spectrum, have been assigned in accordance with new ab initio calculations of the vertical excitation energies and oscillator strengths. Calculations have also been carried out to determine the ionization energies and fine structure of the lowest ionic state of ethyl formate and are compared with a newly recorded He(I) photoelectron spectrum (from 10.1 to 16.1 eV). New vibrational structure is observed in the first photoelectron band. The photoabsorption cross sections have been used to calculate the photolysis lifetime of ethyl formate in the upper stratosphere (20-50 km).

VUV irradiation studies of plasmid DNA in aqueous solution

Interactions of VUV light and DNA samples in aqueous solutions are reported. The damage induced by such radiation is quantified by monitoring both loss of supercoiled DNA and formation of single and double strand breaks using agarose gel electrophoresis. Irradiations were performed using synchrotron VUV photons of 130, 150, 170 and 190 nm. VUV irradiation experiments revealed enhanced damage upon irradiation with 170 nm photons as compared with irradiations with photons of 150 nm and 130 nm. Irradiations carried at 190 nm caused the least damage.

Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics.

Valence and lowest Rydberg electronic states of phenol investigated by synchrotron radiation and theoretical methods

We present the experimental high-resolution vacuum ultraviolet (VUV) photoabsorption spectra of phenol covering for the first time the full 4.3-10.8 eV energy-range, with absolute cross sections determined. Theoretical calculations on the vertical excitation energies and oscillator strengths were performed using time-dependent density functional theory and the equation-of-motion coupled cluster method restricted to single and double excitations level. These have been used in the assignment of valence and Rydberg transitions of the phenol molecule. The VUV spectrum reveals several new features not previously reported in the literature, with particular reference to the 6.401 eV transition, which is here assigned to the 3sσ/σ(∗)(OH)←3π(3a″) transition. The measured absolute photoabsorption cross sections have been used to calculate the photolysis lifetime of phenol in the earths atmosphere (0-50 km).

Early models of DNA damage formation

Quantification of DNA damage, induced by various types of incident radiation as well as chemical agents, has been the subject of many theoretical and experimental studies, supporting the development of modern cancer therapy. The primary observations showed that many factors can lead to damage of DNA molecules. It became clear that the development of experimental techniques for exploring this phenomenon is required. Another problem was simultaneously dealt with, anticipating on how the damage is distributed within the double helix of the DNA molecule and how the single strand break formation and accumulation can influence the lethal double strand break formation. In this work the most important probabilistic models for DNA strand breakage and damage propagation are summarized and compared.Quantification of DNA damage, induced by various types of incident radiation as well as chemical agents, has been the subject of many theoretical and experimental studies, supporting the development of modern cancer therapy. The primary observations showed that many factors can lead to damage of DNA molecules. It became clear that the development of experimental techniques for exploring this phenomenon is required. Another problem was simultaneously dealt with, anticipating on how the damage is distributed within the double helix of the DNA molecule and how the single strand break formation and accumulation can influence the lethal double strand break formation. In this work the most important probabilistic models for DNA strand breakage and damage propagation are summarized and compared.Przeanalizowano jedne z pierwszych modeli opisujących uszkodzenia nici DNA. Przeanalizowano uszkodzenia powstające w pojedynczych i podwojnych niciach, pod wplywem czynnikow fizycznych i chemicznych.

Computational studies of a hypocycloidal electron monochromator

A hypocycloidal electron monochromator (HEM) which uses a uniform axial magnetic field and a cylindrical electric field has been investigated in a computational study using the CPO–3D program. Electron trajectories in the monochromator have been calculated and analysed for an incident electron beam which has a finite angular spread. The energy spread of the electron beam at the exit of the monochromator has been studied as a function of the monochromator parameters. It has been found that the energy resolution of the studied HEM is higher than that of an equivalent trochoidal electron monochromator.