Protecting Orthopaedic Implants from Infection: Antimicrobial Peptide Mel4 Is Non-Toxic to Bone Cells and Reduces Bacterial Colonisation When Bound to Plasma Ion-Implanted 3D-Printed PAEK Polymers.

Even with the best infection control protocols in place, the risk of a hospital-acquired infection of the surface of an implanted device remains significant. A bacterial biofilm can form and has the potential to escape the host immune system and develop resistance to conventional antibiotics, ultimately causing the implant to fail, seriously impacting patient well-being. Here, we demonstrate a 4 log reduction in the infection rate by the common pathogen S. aureus of 3D-printed polyaryl ether ketone (PAEK) polymeric surfaces by covalently binding the antimicrobial peptide Mel4 to the surface using plasma immersion ion implantation (PIII) treatment. The surfaces with added texture created by 3D-printed processes such as fused deposition-modelled polyether ether ketone (PEEK) and selective laser-sintered polyether ketone (PEK) can be equally well protected as conventionally manufactured materials. Unbound Mel4 in solution at relevant concentrations is non-cytotoxic to osteoblastic cell line Saos-2. Mel4 in combination with PIII aids Saos-2 cells to attach to the surface, increasing the adhesion by 88% compared to untreated materials without Mel4. A reduction in mineralisation on the Mel4-containing surfaces relative to surfaces without peptide was found, attributed to the acellular portion of mineral deposition.

A Comparison of In Vivo Bone Tissue Generation Using Calcium Phosphate Bone Substitutes in a Novel 3D Printed Four-Chamber Periosteal Bioreactor.

Autologous bone replacement remains the preferred treatment for segmental defects of the mandible; however, it cannot replicate complex facial geometry and causes donor site morbidity. Bone tissue engineering has the potential to overcome these limitations. Various commercially available calcium phosphate-based bone substitutes (Novabone®, BioOss®, and Zengro®) are commonly used in dentistry for small bone defects around teeth and implants. However, their role in ectopic bone formation, which can later be applied as vascularized graft in a bone defect, is yet to be explored. Here, we compare the above-mentioned bone substitutes with autologous bone with the aim of selecting one for future studies of segmental mandibular repair. Six female sheep, aged 7-8 years, were implanted with 40 mm long four-chambered polyether ether ketone (PEEK) bioreactors prepared using additive manufacturing followed by plasma immersion ion implantation (PIII) to improve hydrophilicity and bioactivity. Each bioreactor was wrapped with vascularized scapular periosteum and the chambers were filled with autologous bone graft, Novabone®, BioOss®, and Zengro®, respectively. The bioreactors were implanted within a subscapular muscle pocket for either 8 weeks (two sheep), 10 weeks (two sheep), or 12 weeks (two sheep), after which they were removed and assessed by microCT and routine histology. Moderate bone formation was observed in autologous bone grafts, while low bone formation was observed in the BioOss® and Zengro® chambers. No bone formation was observed in the Novabone® chambers. Although the BioOss® and Zengro® chambers contained relatively small amounts of bone, endochondral ossification and retained hydroxyapatite suggest their potential in new bone formation in an ectopic site if a consistent supply of progenitor cells and/or growth factors can be ensured over a longer duration.

An omics approach to delineating the molecular mechanisms that underlie the biological effects of physical plasma.

The use of physical plasma to treat cancer is an emerging field, and interest in its applications in oncology is increasing rapidly. Physical plasma can be used directly by aiming the plasma jet onto cells or tissue, or indirectly, where a plasma-treated solution is applied. A key scientific question is the mechanism by which physical plasma achieves selective killing of cancer over normal cells. Many studies have focused on specific pathways and mechanisms, such as apoptosis and oxidative stress, and the role of redox biology. However, over the past two decades, there has been a rise in omics, the systematic analysis of entire collections of molecules in a biological entity, enabling the discovery of the so-called "unknown unknowns." For example, transcriptomics, epigenomics, proteomics, and metabolomics have helped to uncover molecular mechanisms behind the action of physical plasma, revealing critical pathways beyond those traditionally associated with cancer treatments. This review showcases a selection of omics and then summarizes the insights gained from these studies toward understanding the biological pathways and molecular mechanisms implicated in physical plasma treatment. Omics studies have revealed how reactive species generated by plasma treatment preferentially affect several critical cellular pathways in cancer cells, resulting in epigenetic, transcriptional, and post-translational changes that promote cell death. Finally, this review considers the outlook for omics in uncovering both synergies and antagonisms with other common cancer therapies, as well as in overcoming challenges in the clinical translation of physical plasma.

Monte Carlo calculations of radiotherapy dose distributions within and around orthopaedic implants.

Background and purpose: Cancer patients often require a titanium orthopaedic implant to support or replace lost bone. In radiation treatment, the dose distribution is perturbed causing regions of high and low dose at material interfaces. Since the survival of integrating bone tissue is critical to implant success, the aim of this study was to determine the dose distribution in and around the scaffold, when constructed from titanium or Poly-ether-ether-ketone (PEEK). Materials and methods: The dose distributions in the pores and along boundaries for three implant scaffold designs were calculated using Monte-Carlo methods in Geant4/GATE, with the material taken as titanium or PEEK. The 3D dose distributions were analysed in MATLAB and segmented using image masks, yielding the dose distributions in key regions of interest. To evaluate the effect of the predicted dose perturbations, the cell survival was calculated using the linear-quadratic model for SAOS-2 cells (bone) using experimentally determined radiation response data. Results: High dose gradients were found along the boundaries of the titanium implants, but not for the corresponding PEEK implants. The dose to the internal cavities of the titanium implants was enhanced by 10-15% near the proximal interface whereas for PEEK, there was no significant dose perturbation. The predicted perturbation caused by the titanium implant was shown to decrease the survival for SAOS-2 cells by 7% which was not found for the PEEK implants. Conclusion: PEEK was shown to be a more favourable orthopaedic implant material over titanium for cancer patients considering radiation therapy.

Radiation responses of cancer and normal cells to split dose fractions with uniform and grid fields: increasing the therapeutic ratio.

PURPOSE: Radiation treatment of cancer is usually delivered in a prescribed sequence of dose fractions within which the dependence of dose on time is determined by the treatment plan. New techniques, such as stereotactic body radiation therapy (SBRT) and image guided radiation therapy (IGRT) have been introduced with the motivation of improving therapeutic outcomes, with the consequence that the time dependence of the dose within a fraction is modified. Here, we test whether an increased toxicity to cancer cells arises when a radiation treatment fraction is delivered in two equal parts, allowing time for the expression of factors, for example, RONS and cytokines, in response to the first dose which may sensitize cells to the second dose. A medium time delay between 15 and 60 minutes is proposed to allow factors to be expressed before repair takes place. A grid field is used to enhance diffusion of the factors. MATERIALS AND METHODS: The cell lines used in the study were two prostate cancers (LNCaP and DU 145), a normal prostate (PNT1A), a non-small cell lung cancer (NCI-H460), and a glioma (Hs 683). Uniform or spatially modulated grid fields, delivering the same mean dose, were used. The results for the clonogenic survival fractions were grouped into a 'short' delay (under 10 minutes) and a 'medium' delay (between 15 and 60 minutes). RESULTS: The medium delay with a grid field yielded a significant increase in toxicity for the four cancer cell lines. The medium delay with a uniform field gave a significant increase in toxicity for the two prostate cancer cell lines. A highly significant increase was found in the therapeutic ratio, defined as the ratio of the survival of prostate normal to prostate cancer cells. CONCLUSIONS: The findings show that the intra-fractional dose schedule with medium time delay offers an opportunity to increase the toxicity of radiation to cancer cells, relative to a single radiation delivery. For all cancer cell lines, a grid field gives a greater toxic effect than a uniform field. The split dose treatment offers an increase in cancer toxicity while preserving normal cells, improving the outcomes of a treatment.

Cancer treatment with gas plasma and with gas plasma-activated liquid: positives, potentials and problems of clinical translation.

Gas plasmas, created in atmospheric pressure conditions, both thermal (hot) and non-thermal (cold) are emerging as useful tools in medicine. During surgery, hot gas plasmas are useful to reduce thermal damage and seal blood vessels. Gas plasma pens use cold gas plasma to produce reactive chemical species with selective action against cancers, which can be readily exposed in surgery or treated from outside of the body. Solutions activated by cold gas plasma have potential as a novel treatment modality for treatment of less readily accessible tumours, or those with high metastatic potential. This review summarises the preclinical and clinical trial evidence currently available, as well as the challenges for translation of direct gas plasma and gas plasma-activated solution treatment into regular practice.

Transcriptional regulation of G2/M regulatory proteins and perturbation of G2/M Cell cycle transition by a traditional Chinese medicine recipe.

ETHNOPHARMACOLOGICAL RELEVANCE: Hedyotis diffusa Willd. (H) and Scutellaria barbata D.Don (S) are ancient anti-cancer Chinese herb medicines. When combined, known as HS, it is one of the most commonly prescribed Chinese Medicines for cancer patients today in China. AIM OF THE STUDY: The prevention of disease progression is a dominant concern for the growing number of men with prostate cancer. The purpose of this work is to evaluate the action and mode of action of Chinese Medicine recipe HS in inhibiting prostate cancer progression in preclinical models. METHODS: Effects of HS were analyzed in prostate cancer cell lines by evaluating proliferation, cell cycle profile, DNA damage and key regulators responsible for G2 to M phase transition. The transcriptional activities of these regulators were determined by RT-PCR and ChIP. The efficacy of HS in vitro was validated in an animal model. RESULTS: HS treatment was observed to reduce DNA content and accumulated prostate cancer cells at the G2/M phase. Immunolabeling for phospho-Histone H3 in association with nocodazole to capture mitotic cells confirmed that HS impeded G2 to M transition. After excluding DNA damage-induced G2 arrest, it was revealed that HS reduced expression of Cyclin B1, CDK1, PLK1 and Aurora A at both protein and mRNA levels, with concomitant reduction of H3K4 tri-methylation at their promoter-regions. Animals that received oral administration of HS with a dosage relevant to clinical application showed reduced tumor volume and weight with a reduction of Cyclin B1, CDK1, PLK1 and Aurora A protein levels. CONCLUSIONS: HS acts by impeding the G2 to M transition of prostate cancer cells. It is likely that the mode of action is transcriptionally suppressing proteins governing mitotic entry, without eliciting significant DNA damage.

Imaging prior to radiotherapy impacts in-vitro survival.

BACKGROUND AND PURPOSE: Cone Beam Computed Tomography (CBCT) is routinely used in radiotherapy to identify the position of the target volume. The aim of this study was to determine whether the CBCT dose, when followed by the treatment, influences the therapeutic outcomes as determined by in-vitro clonogenic cell survival in a radiobiological experiment. MATERIALS AND METHODS: Human cell lines, four cancer and one normal, were exposed to a 6 MV photon beam, produced by a linear accelerator. For half of each sample, a prior imaging dose was delivered using the on-board CBCT. A sample size of n = 103 was used to achieve statistical power. RESULTS: The experimental group of cell lines exposed to CBCT imaging prior to treatment exhibited a reduction in mean cancer cell survival of ~17 times (p = 0.02) greater than predicted from the average dose response and equivalent to more than 5% of the therapeutic dose, compared to 11 times greater than predicted for normal cells (n.s.). CONCLUSION: The greater than predicted reduction in survival resulting from the additional CBCT dose is consistent with radiation-induced bystander effects.

Single Step Plasma Process for Covalent Binding of Antimicrobial Peptides on Catheters To Suppress Bacterial Adhesion.

Catheter-associated biofilms are responsible for a large fraction of hospital acquired infections. Antimicrobial surface coating on catheters providing prevention at source is extensively studied to reduce bacterial adhesion. Antimicrobial peptides such as melimine and Mel4, covalently linked to surfaces, have shown excellent potential in animal and human studies to suppress infection without toxicity. Covalent binding of the peptides on catheter surfaces improves efficacy but so far has been implemented using multistep wet chemical coupling that will impede widespread adoption. Here we demonstrate plasma immersion ion implantation (PIII) as a single step treatment that covalently couples antimicrobial peptides to polyvinyl chloride (PVC). Strong antimicrobial activity was demonstrated by higher than 3 log kill of S. aureus. A variant of the process was demonstrated as an antimicrobial treatment for chemically inert glass surfaces. Covalent coupling was rigorously tested by stringent SDS washing. We further demonstrated that the plasma treatment can effectively functionalize both internal and external surfaces of catheter tubing, reducing 99% of bacterial adhesion. The process is feasible as a patient-safe treatment for treating various types of catheters and is suitable for commercial mass production. In a logical extension of the work, the process could be adapted to bone replacement scaffolds of all types including metallic, polymeric, and ceramic.

Women and men in the Australasian College of Physical Scientists and Engineers in Medicine: workforce survey.

A survey was designed to determine aspirations, motivations and workplace experiences of both female and male members of the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM). The survey collected both quantitate and qualitative data, including open ended questions. This paper reports the survey's qualitative results. The research was approved by Ethics at University of South Australia and endorsed by ACPSEM. All 205 women (30% of total membership) and 440 men were invited to complete the survey online. The data for the qualitative analysis were responses to open-ended questions within the survey. 102 women and 150 men completed surveys were received, with 66 surveys analysed, before data saturation was reached. The survey revealed a number of themes that reflect concerns and opportunities identifying the direction for improving work-life balance and gender equity within the medical physics profession in Australasia. Issues around managing challenging workloads and professional development were amplified for women with children and child-rearing responsibilities, directly contributing to a reduction in work capacity and a reorientation of work-life priorities. The survey provides direction for strategies to improve work-life balance and enable equitable engagement in the profession. The first is to identify and develop role models that actively model successful work-life balance and flexibility in gender roles and in professional conduct. The second is to improve the management skills of current and emerging administrators, advocating for improved work conditions for medical physics professionals at an organisation level. Finally, efforts need to be made to establish flexible professional development and career progression opportunities amongst those that are unable to commit to large workloads, which is common for those with child-rearing responsibilities. The realisation of these strategic goals will reduce the identified barriers to full female participation in the workforce, and shift gender-based subcultures within the workplace.

Models for the bystander effect in gradient radiation fields: Range and signalling type.

Bystander responses to radiation are responsible for a significant fraction of cell death, but are not included in the conventional linear-quadratic (LQ) radiobiological model. Strong dose gradients in radiation fields affect the distribution of bystander signals and can be used to decrease the survival of cancer cells. Predictive models incorporating bystander effects are needed to design the dose gradients in modulated fields to improve cancer treatments. Fundamental questions concern the nature and range of bystander signalling. Some authors propose bystander signals are carried by diffusing molecular factors expressed into the extracellular medium and that strong dose gradients drive their diffusion. Others propose bystander effects occur between neighbouring cells through gap-junctions, leaving no universal agreement. Here we test three assumptions concerning the effective range of bystander signals using both average and local measures of survival. Model 1 assumes short range signalling (e.g. gap-junction mediated) proportional to the local dose gradient, without relying on diffusion across the extracellular medium; Model 2 assumes metabolite diffusion governed by Fick's second law with either negative or both signs of bystander effect; Model 3 assumes that the extent of signal production is dependent on the average of the dose gradient over the field and that the signals have long range distribution. A single bystander parameter for each model was fitted to observed average survival of cancer cells in uniform and modulated fields. All models gave better fits than the classical LQ model. Model 2 fitted best with one sign of bystander effect on survival. Model 3 gave the best overall fit of average survival. The models were then used to predict local survival and survival as a function of dose in modulated fields, using independent datasets, without changing the bystander parameter. Model 3 gave the best overall prediction. This study demonstrates that the bystander effect can be controlled by design of the radiation field modulation.

Sensitization of prostate cancer to radiation therapy: Molecules and pathways to target.

Radiation therapy is used to treat cancer by radiation-induced DNA damage. Despite the best efforts to eliminate cancer, some cancer cells survive irradiation, resulting in cancer progression or recurrence. Alteration in DNA damage repair pathways is common in cancers, resulting in modulation of their response to radiation. This article focuses on the recent findings about molecules and pathways that potentially can be targeted to sensitize prostate cancer cells to ionizing radiation, thereby achieving an improved therapeutic outcome.

Radiation dosimetry in cell biology: comparison of calculated and measured absorbed dose for a range of culture vessels and clinical beam qualities.

PURPOSE: Cell culture studies are frequently used to evaluate the effects of cancer treatments such as radiotherapy, hormone therapy, chemotherapy, nanoparticle enhancement, and to determine any synergies between the treatments. To achieve valid results, the absorbed dose of each therapy needs to be well known and controlled. In this study, we aim to determine the uncertainty associated with radiation exposure in different experimental conditions. MATERIALS AND METHODS: We have performed an in-depth evaluation of the absorbed dose and dose distribution that would be delivered to a cell sample when cultivated in a number of the more popular designs of culture vessels. We focus on exposure to two beam types: a kilovoltage x-ray beam and a megavoltage photon beam, both of which are routinely used to treat cancer patients in the clinical environment. CONCLUSIONS: Our results identify large variations of up to 16% in the absorbed dose across multi-well culture plates, which if ignored in radiobiological experiments, have the potential to lead to erroneous conclusions.

Dosimetric consequences of gold nanoparticle clustering during photon irradiation.

PURPOSE: The radiation dose enhancement caused by introducing gold nanoparticles (GNP) into cells can increase the dose locally absorbed. A disconnect between experimentally determined survival and dose enhancements predicted by Monte Carlo simulations on macroscopic scales, suggests small-scale energy deposition patterns play an important role in GNP dose enhancement. Clustering of the GNPs could potentially alter small-scale energy deposition patterns. Here we use Monte Carlo simulations to quantify energy deposition patterns in the presence of clustered GNPs and address the question of whether clustering of the nanoparticles affects the energy deposition patterns and ultimately cellular response. METHODS: Using the PENELOPE Monte Carlo code, we examine the absorption of energy in the environment of a single irradiated GNP following its interaction with a set of primary monoenergetic photon beams. We introduce successive GNPs to form a cluster about the particle in which the primary photon interactions occur and report on the energy deposited locally (within a 500 nm radius) and nonlocally (beyond 500 nm) in the surrounding water-equivalent medium as a function of the number of additional GNPs and the packing geometry they assume. RESULTS: When additional GNPs cluster in tightly packed formations about a GNP in which an incident photon interacts, both the energy deposited locally and released nonlocally are reduced relative to the case where other GNPs are not present. The degree of the reduction depends on incident photon energy, the number of GNPs added to the cluster, and the packing geometry. With 90 additional GNPs in a hexagonal close packing (HCP) cluster about a directly irradiated test particle, the local energy deposition was reduced to 29% (of the value in the absence of neighbors) in the most extreme monoenergetic case. Energy released into the nonlocal volume was most affected by the cluster for low-incident photon energies (< 40 keV), where reductions to 26% of the value in the absence of a cluster were shown. The packing geometry mitigated these results. When the irradiated GNP was on the periphery of the HCP cluster, or when the cluster was confined to a plane, the observed effects were weaker and when an equal number of GNPs were uniformly distributed in the local volume, the changes were trivial (less than 2%). CONCLUSIONS: The findings provide grounds for reconciling the observations of cell survival with Monte Carlo predictions of GNP dose enhancement. This work is significant because it demonstrates that GNP clustering needs to be understood and accounted to optimize local dose enhancement.

Grid therapy using high definition multileaf collimators: realizing benefits of the bystander effect.

BACKGROUND: In microbeam radiotherapy (MRT), parallel arrays of high-intensity synchrotron x-ray beams achieve normal tissue sparing without compromising tumor control. Grid-therapy using clinical linacs has spatial modulation on a larger scale and achieves promising results for palliative treatments of bulky tumors. The availability of high definition multileaf collimators (HDMLCs) with 2.5 mm leaves provides an opportunity for grid-therapy to more closely approach MRT. However, challenges to the wider implementation of grid-therapy remain because spatial modulation of the target volume runs counter to current radiotherapy practice and mechanisms for the beneficial effects of MRT are not fully understood. Without more knowledge of cell dose responses, a quantitative basis for planning treatments is difficult. The aim of this study is to determine if therapeutic benefits of MRT can be achieved using a linac with HDMLCs and if so, to develop a predictive model to support treatment planning. MATERIAL AND METHODS: HD120-MLCs of a Varian Novalis TXTM were used to generate grid patterns of 2.5 and 5.0 mm spacing, which were characterized dosimetrically using GafchromicTM EBT3 film. Clonogenic survival of normal (HUVEC) and cancer (NCI-H460, HCC-1954) cell lines following irradiation under the grid and open fields using a 6 MV photon beam were compared in-vitro for the same average dose. RESULTS AND CONCLUSIONS: Relative to an open field, survival of normal cells in a 2.5 mm striped field was the same, while the survival of both cancer cell lines was significantly lower. A mathematical model was developed to incorporate dose gradients of the spatial modulation into the standard linear quadratic model. Our new bystander extended LQ model assumes spatial gradients drive the diffusion of soluble factors that influence survival through bystander effects, successfully predicting the experimental results that show an increased therapeutic ratio. Our results challenge conventional radiotherapy practice and propose that additional gain can be realized by prescribing spatially modulated treatments to harness the bystander effect.

Small field correction factors for the IBA Razor.

The IBA Razor diode supersedes the IBA SFD and is intended for use in small fields. However, its behaviour in small fields has not yet been quantified. In this work, we examine the response of the Razor diode against the air core scintillation dosimeter (FOD) and Gafchromic film in photon beams from three Varian linac beams. Fields between 4mm and 30mm in width were measured, both with and without a flattening filter and at two energies. The Razor exhibited an over-response of up to 4.5% for MLC collimated fields and 7.1% for stereotactic cone collimated fields. The presence of the flattening filter altered the over-response by up to 1.5%. The small field correction factors are tabulated and agree with the mathematical relation of Liu et al. (2014). Four samples of the Razor were used, two having received a significant prior dose. The correction factors for the four samples differed and may depend on their dose history.

Small field detector correction factors: effects of the flattening filter for Elekta and Varian linear accelerators.

Flattening filter-free (FFF) beams are becoming the preferred beam type for stereotactic radiosurgery (SRS) and stereotactic ablative radiation therapy (SABR), as they enable an increase in dose rate and a decrease in treatment time. This work assesses the effects of the flattening filter on small field output factors for 6 MV beams generated by both Elekta and Varian linear accelerators, and determines differences between detector response in flattened (FF) and FFF beams. Relative output factors were measured with a range of detectors (diodes, ionization cham-bers, radiochromic film, and microDiamond) and referenced to the relative output factors measured with an air core fiber optic dosimeter (FOD), a scintillation dosimeter developed at Chris O'Brien Lifehouse, Sydney. Small field correction factors were generated for both FF and FFF beams. Diode measured detector response was compared with a recently published mathematical relation to predict diode response corrections in small fields. The effect of flattening filter removal on detector response was quantified using a ratio of relative detector responses in FFF and FF fields for the same field size. The removal of the flattening filter was found to have a small but measurable effect on ionization chamber response with maximum deviations of less than ± 0.9% across all field sizes measured. Solid-state detectors showed an increased dependence on the flattening filter of up to ± 1.6%. Measured diode response was within ± 1.1% of the published mathematical relation for all fields up to 30 mm, independent of linac type and presence or absence of a flattening filter. For 6 MV beams, detector correction factors between FFF and FF beams are interchangeable for a linac between FF and FFF modes, providing that an additional uncertainty of up to ± 1.6% is accepted.

Characterization of a new unshielded diode for small field dosimetry under flattening filter free beams.

PURPOSE: To characterize the performance of a new unshielded silicon diode (Razor-IBA) for dose measurements in small flattening filter free beams. METHODS: The Razor has an active volume of 0.6 mm in diameter and 20 µm in length. The detector response stability in measured dose, dose rate, dose per pulse, and dark current were evaluated. The detector response in square fields (0.6-5.0 cm) was determined using PDD curves, axial beam profiles and output ratios. The performances were compared to that of the previously available SFD-IBA and PFD-IBA diodes. RESULTS AND DISCUSSION: The Razor short term stability relative to the SFD was much improved (<±0.1% after 1.2 kGy). The linearity was <±1% (0.05-30 Gy range) and the dose rate dependence was <±0.5% (4-24 Gy/min range). The dose per pulse dependence was <±0.7% (0.08-0.21 cGy/pulse range). The PDDs measured with Razor and PFD differed <1%. A larger dark current was observed with increase in dose (0.0025 pA/Gy) compared to the SFD (0.0002 pA/Gy). This characteristic is attributed to an increased concentration of recombination centers. The beam profile showed good agreement with the SFD. Penumbra differences were <±0.3 mm relative to PFD, with a slight overestimation of the tails (<1%), due to the absence of diode shielding. Output ratios were in good agreement for fields up to 5 × 5 cm(2) (<1%). CONCLUSIONS: The Razor diode has the same spatial resolution and performance reliability as its predecessor (SFD), but exhibits the additional advantage of improved stability. These features make the Razor diode detector a good candidate for small field dosimetry.

Dose enhancement and cytotoxicity of gold nanoparticles in colon cancer cells when irradiated with kilo- and mega-voltage radiation.

Despite major advances in the field of radiotherapy, healthy tissue damage continues to constrain the dose that can be prescribed in cancer therapy. Gold nanoparticles (GNPs) have been proposed as a solution to minimize radiation-associated toxicities by enhancing the radiation dose delivered locally to tumor cells. In the current study, we investigated the application of third-generation GNPs in two-dimensional (2D) and three-dimensional (3D) cell cultures and whether there is synergy between the nanoparticles and kilo- or mega-voltage radiation to cause augmented cytotoxicity. The 10-nm GNPs were found to be nontoxic in both 2D and 3D in vitro cultures of colon cancer cells at concentrations of up to 10-25 µg/ml. There was a significant increase in cell survival fraction reduction following exposure to 1 Gy of kilo-voltage (18.3%) and 2 Gy of mega-voltage (35.3%) radiation when the cells were incubated with 50 µg/ml of GNPs. The biocompatibility of the GNPs combined with their substantial synergy with radiation encourages further investigations into their application in targeted cancer treatment.