Computational Modeling and Clonogenic Assay for Radioenhancement of Gold Nanoparticles Using 3D Live Cell Images

Abstract

Radioenhancement of gold nanoparticles (GNPs) has shown great potential for increasing the therapeutic efficiency of radiotherapy. Here we report on a computational model of radiation response, which was developed to predict the survival curves of breast cancer cells incubated with GNPs. The amount of GNP uptake was estimated using inductively coupled plasma-mass spectroscopy, and the three-dimensional (3D) intracellular distribution of GNPs was obtained using optical diffraction tomography. The developed computational model utilized the 3D live cell imaging and recent Monte Carlo techniques to calculate microscopic dose distributions within the cell. Clonogenic assays with and without GNPs were performed to estimate the radioenhancement for 150 kVp X rays in terms of cell survival fractions. Measured cell survival fractions were comparable with the computational model.

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes

“…Due to their presumed biocompatibility, their strong photoelectric absorption coefficient, and the emission of Auger and Coster-Kronig (C-K) electrons, gold nanoparticles (GNPs) (Z = 79) have been extensively investigated for several years as possible agents for a selective amplification of the radiation dose in tumors [4]. This concept is known as "gold nanoparticle assisted radiation therapy" (GNRT) [5][6][7][8][9]. The first successful experiment using GNPs to increase the radiosensitivity of tumors in mice irradiated by X-rays [10] stimulated extended investigations, by experiments [11][12][13][14][15][16][17] and computational Monte Carlo (MC) simulations, into the effects of GNPs when using different types of radiation such as kilovoltage X-rays [18][19][20][21][22][23][24][25][26][27][28][29], megavoltage X-rays, protons and heavy ions [30][31][32].…”

Optical quantification of intracellular mass density and cell mechanics in 3D mechanical confinement

“…This is different from our 2D results as well as compared to recent 2D data on RI distribution across various cell lines including MDA-MB-231, where it was shown that cells cytoplasm have higher RI than their nuclei using a wide variety of microscopy techniques. [23][24][25][26][27][28]59,60 Such discrepancy might be attributed to differences in cytoskeletal and/or nuclear morphologies in 2D compared to 3D. Cells on 2D substrates spread out and elongate, displaying a forced ventral-dorsal polarity compared to the non-polarized shape of cells in 3D.…”

Radiosensitization by Au‐nanofilm at micrometer level using confocal Raman spectroscopy

“…10 From a clinical perspective; other studies have studied the microscopic dose distribution to estimate the cell survival fraction. 11,12 Mirza et al first employed different GNF sizes and energy beams to calculate the dose enhancement factor in the whole thickness of EBT-XD active layer using Raman spectroscopy. 13 In the last few decades, Monte Carlo simulations have been widely used to estimate the radio-enhancement by metal nanoparticles at the micrometer level.…”