Modelling direct DNA damage for gold nanoparticle enhanced proton therapy

A facile method for in situ fabrication of three-dimensional gold nanoparticles micropatterns throughout a polyethylene glycol hydrogel substrate has been developed by combining photochemical synthesis of gold nanoparticles with photolithography technology.

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Modelling Spatial Scales of Dose Deposition and Radiolysis Products from Gold Nanoparticle Sensitisation of Proton Therapy in A Cell: From Intracellular Structures to Adjacent Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21124431 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4431

Author(s):

Dylan Peukert ◽

Ivan Kempson ◽

Michael Douglass ◽

Eva Bezak

Keyword(s):

Gold Nanoparticle ◽

Proton Therapy ◽

Nuclear Membrane ◽

Cell Model ◽

Spatial Scales ◽

Permeable Membrane ◽

Membrane Absorption ◽

Cellular Targets ◽

A Cell ◽

Dose Deposition

Gold nanoparticle (GNP) enhanced proton therapy is a promising treatment concept offering increased therapeutic effect. It has been demonstrated in experiments which provided indications that reactive species play a major role. Simulations of the radiolysis yield from GNPs within a cell model were performed using the Geant4 toolkit. The effect of GNP cluster size, distribution and number, cell and nuclear membrane absorption and intercellular yields were evaluated. It was found that clusters distributed near the nucleus increased the nucleus yield by 91% while reducing the cytoplasm yield by 7% relative to a disperse distribution. Smaller cluster sizes increased the yield, 200 nm clusters had nucleus and cytoplasm yields 117% and 35% greater than 500 nm clusters. Nuclear membrane absorption reduced the cytoplasm and nucleus yields by 8% and 35% respectively to a permeable membrane. Intercellular enhancement was negligible. Smaller GNP clusters delivered near sub-cellular targets maximise radiosensitisation. Nuclear membrane absorption reduces the nucleus yield, but can damage the membrane providing another potential pathway for biological effect. The minimal effect on adjacent cells demonstrates that GNPs provide a targeted enhancement for proton therapy, only effecting cells with GNPs internalised. The provided quantitative data will aid further experiments and clinical trials.

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EP-1613: Modelling DNA damage on gold nanoparticle enhanced proton therapy

Radiotherapy and Oncology ◽

10.1016/s0167-8140(17)32048-0 ◽

2017 ◽

Vol 123 ◽

pp. S872

Author(s):

M. Sotiropoulos ◽

N.T. Henthorn ◽

J.W. Warmenhoven ◽

R.I. Mackay ◽

K.J. Kirkby ◽

...

Keyword(s):

Dna Damage ◽

Gold Nanoparticle ◽

Proton Therapy

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Gold Nanoparticle Enhanced Proton Therapy: Monte Carlo Modeling of Reactive Species’ Distributions Around a Gold Nanoparticle and the Effects of Nanoparticle Proximity and Clustering

International Journal of Molecular Sciences ◽

10.3390/ijms20174280 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4280 ◽

Cited By ~ 5

Author(s):

Peukert ◽

Kempson ◽

Douglass ◽

Bezak

Keyword(s):

Monte Carlo ◽

Gold Nanoparticle ◽

Proton Therapy ◽

Species Distributions ◽

Reactive Species ◽

Monte Carlo Modeling ◽

Chemical Damage ◽

Extended Range ◽

Biological Target ◽

A Cell

Gold nanoparticles (GNPs) are promising radiosensitizers with the potential to enhance radiotherapy. Experiments have shown GNP enhancement of proton therapy and indicated that chemical damage by reactive species plays a major role. Simulations of the distribution and yield of reactive species from 10 ps to 1 µs produced by a single GNP, two GNPs in proximity and a GNP cluster irradiated with a proton beam were performed using the Geant4 Monte Carlo toolkit. It was found that the reactive species distribution at 1 µs extended a few hundred nm from a GNP and that the largest enhancement occurred over 50 nm from the nanoparticle. Additionally, the yield for two GNPs in proximity and a GNP cluster was reduced by up to 17% and 60% respectively from increased absorption. The extended range of action from the diffusion of the reactive species may enable simulations to model GNP enhanced proton therapy. The high levels of absorption for a large GNP cluster suggest that smaller clusters and diffuse GNP distributions maximize the total radiolysis yield within a cell. However, this must be balanced against the high local yields near a cluster particularly if the cluster is located adjacent to a biological target.

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EP-1997: Monte Carlo simulations of direct DNA damage on gold nanoparticle enhanced proton therapy

Radiotherapy and Oncology ◽

10.1016/s0167-8140(18)32306-5 ◽

2018 ◽

Vol 127 ◽

pp. S1086

Author(s):

M. Sotiropoulos ◽

N.T. Henthorn ◽

J.W. Warmenhoven ◽

R.I. Mackay ◽

K.J. Kirkby ◽

...

Keyword(s):

Dna Damage ◽

Monte Carlo ◽

Monte Carlo Simulations ◽

Gold Nanoparticle ◽

Proton Therapy

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Interference of Gold Nanoparticles with In vitro Endotoxin Detection Assays

Current Nanoscience ◽

10.2174/1573413715666181212120013 ◽

2020 ◽

Vol 16 (2) ◽

pp. 204-213 ◽

Cited By ~ 1

Author(s):

Melissa A. Vetten ◽

Mary Gulumian

Keyword(s):

Gold Nanoparticles ◽

Gold Nanoparticle ◽

Surface Reactivity ◽

In Vitro Assays ◽

Limulus Amebocyte Lysate ◽

Chromogenic Assay ◽

Nanoparticle Suspensions ◽

Endotoxin Contamination ◽

Factor C

Background: Endotoxin-free engineered nanoparticle suspensions are imperative for their successful applications in the field of nanomedicine as well as in the investigations in their toxicity. Gold nanoparticles are known to interfere with various in vitro assays due to their optical properties and potential for surface reactivity. In vitro endotoxin testing assays are known to be susceptible to interference caused by the sample being tested. Objective: This study aimed to identify a preferred assay for the testing of endotoxin contamination in gold nanoparticle suspensions. Methods: The interference by gold nanoparticles on three assays namely, the commonly used limulus amebocyte lysate chromogenic assay, the limulus amebocyte lysate gel-clot method, and the less common recombinant Factor C (rFC) assay, was tested. Results: Possible interference could be observed with all three assays. The interference with the absorbance- based chromogenic assay could not be overcome by dilution; whilst the qualitative nature of the gel-clot assay excluded the possibility of distinguishing between a false positive result due to enhancement of the sensitivity of the assay, and genuine endotoxin contamination. However, interference with the rFC assay was easily overcome through dilution. Conclusion: The rFC assay is recommended as an option for endotoxin contamination detection in gold nanoparticle suspensions.

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CRISPR/Cas12a-mediated gold nanoparticle aggregation for colorimetric detection of SARS-CoV-2

Chemical Communications ◽

10.1039/d1cc02546e ◽

2021 ◽

Author(s):

Yiren Cao ◽

Jinjun Wu ◽

Bo Pang ◽

Hongquan Zhang ◽

X. Chris Le

Keyword(s):

Gold Nanoparticles ◽

Gold Nanoparticle ◽

Colorimetric Detection ◽

Isothermal Amplification ◽

Nanoparticle Aggregation ◽

Cleavage Activity ◽

Gold Nanoparticle Aggregation

The trans-cleavage activity of the target-activated CRISPR-Cas12a liberated an RNA crosslinker from a molecular transducer, which facilitated assembly of gold nanoparticles. Integration of the molecular transducer with isothermal amplification and...

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Fluorescence biosensor for Salmonella typhimurium detection in food based on nano-self-assembly of alendronic acid modified upconversion and gold nanoparticles

Analytical Methods ◽

10.1039/d1ay00493j ◽

2021 ◽

Author(s):

Min Chen ◽

Leiqing Pan ◽

K. Tu

Keyword(s):

Gold Nanoparticles ◽

Salmonella Typhimurium ◽

Gold Nanoparticle ◽

Alendronic Acid ◽

Self Assembly ◽

Upconversion Nanoparticles ◽

Fluorescent Biosensor ◽

Fluorescence Biosensor

A simple and quick responsive fluorescent biosensor for Salmonella typhimurium detection based on the recognition of aptamer coupled with alendronic acid (ADA)@upconversion nanoparticles (UCNPs) and gold nanoparticle (AuNPs) has been...

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Enhanced Extracellular Synthesis of Gold Nanoparticles by Soluble Extracts from Escherichia coli Transformed with Rhizobium tropici Phytochelatin Synthase Gene

Metals ◽

10.3390/met11030472 ◽

2021 ◽

Vol 11 (3) ◽

pp. 472

Author(s):

Qunying Yuan ◽

Manjula Bomma ◽

Zhigang Xiao

Keyword(s):

Gold Nanoparticles ◽

Gold Nanoparticle ◽

Synthesis Method ◽

Nanoparticle Synthesis ◽

Morphological Properties ◽

Phytochelatin Synthase ◽

Rhizobium Tropici ◽

Whole Cells ◽

E Coli ◽

Recombinant Cells

Phytochelatins, the enzymatic products of phytochelatin synthase, play a principal role in protecting the plants from heavy metal and metalloid toxicity due to their ability to scavenge metal ions. In the present study, we investigated the capacity of soluble intracellular extracts from E. coli cells expressing R. tropici phytochelatin synthase to synthesize gold nanoparticle. We discovered that the reaction mediated by soluble extracts from the recombinant E. coli cells had a higher yield of gold nanoparticles, compared to that from the control cells. The compositional and morphological properties of the gold nanoparticles synthesized by the intracellular extracts from recombinant cells and control cells were similar. In addition, this extracellular nanoparticle synthesis method produced purer gold nanoparticles, avoiding the isolation of nanoparticles from cellular debris when whole cells are used to synthesize nanoparticles. Our results suggested that phytochelatins can improve the efficiency of gold nanoparticle synthesis mediated by bacterial soluble intracellular extracts, and the potential of extracellular nanoparticle synthesis platform for the production of nanoparticles in large quantity and pure form is worth further investigation.

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