title: Investigation of the effects of cell model and subcellular location of gold nanoparticles on nuclear dose enhancement factors using Monte Carlo simulation.
abstract: OBJECTIVE
  The authors' aims were to model how various factors influence radiation dose enhancement by gold nanoparticles (AuNPs) and to propose a new modeling approach to the dose enhancement factor (DEF).
  
  
  METHODS
  The authors used Monte Carlo N-particle (MCNP 5) computer code to simulate photon and electron transport in cells. The authors modeled human breast cancer cells as a single cell, a monolayer, or a cluster of cells. Different numbers of 5, 30, or 50 nm AuNPs were placed in the extracellular space, on the cell surface, in the cytoplasm, or in the nucleus. Photon sources examined in the simulation included nine monoenergetic x-rays (10-100 keV), an x-ray beam (100 kVp), and (125)I and (103)Pd brachytherapy seeds. Both nuclear and cellular dose enhancement factors (NDEFs, CDEFs) were calculated. The ability of these metrics to predict the experimental DEF based on the clonogenic survival of MDA-MB-361 human breast cancer cells exposed to AuNPs and x-rays were compared.
  
  
  RESULTS
  NDEFs show a strong dependence on photon energies with peaks at 15, 30/40, and 90 keV. Cell model and subcellular location of AuNPs influence the peak position and value of NDEF. NDEFs decrease in the order of AuNPs in the nucleus, cytoplasm, cell membrane, and extracellular space. NDEFs also decrease in the order of AuNPs in a cell cluster, monolayer, and single cell if the photon energy is larger than 20 keV. NDEFs depend linearly on the number of AuNPs per cell. Similar trends were observed for CDEFs. NDEFs using the monolayer cell model were more predictive than either single cell or cluster cell models of the DEFs experimentally derived from the clonogenic survival of cells cultured as a monolayer. The amount of AuNPs required to double the prescribed dose in terms of mg Au/g tissue decreases as the size of AuNPs increases, especially when AuNPs are in the nucleus and the cytoplasm. For 40 keV x-rays and a cluster of cells, to double the prescribed x-ray dose (NDEF = 2) using 30 nm AuNPs, would require 5.1 ± 0.2, 9 ± 1, 10 ± 1, 10 ± 1 mg Au/g tissue in the nucleus, in the cytoplasm, on the cell surface, or in the extracellular space, respectively. Using 50 nm AuNPs, the required amount decreases to 3.1 ± 0.3, 8 ± 1, 9 ± 1, 9 ± 1 mg Au/g tissue, respectively.
  
  
  CONCLUSIONS
  NDEF is a new metric that can predict the radiation enhancement of AuNPs for various experimental conditions. Cell model, the subcellular location and size of AuNPs, and the number of AuNPs per cell, as well as the x-ray photon energy all have effects on NDEFs. Larger AuNPs in the nucleus of cluster cells exposed to x-rays of 15 or 40 keV maximize NDEFs.
authors: Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
authors: Zhongli
authors: Z
authors: Cai
authors: Jean-Philippe
authors: JP
authors: Pignol
authors: Niladri
authors: N
authors: Chattopadhyay
authors: Yongkyu Luke
authors: YL
authors: Kwon
authors: Eli
authors: E
authors: Lechtman
authors: Raymond M
authors: RM
authors: Reilly
mesh_terms: D001918:Brachytherapy / Q000379:methods; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D002467:Cell Nucleus / Q000000981:diagnostic imaging; D003593:Cytoplasm / Q000000981:diagnostic imaging; D004583:Electrons; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry*; D009010:Monte Carlo Method; D010165:Palladium / Q000737:chemistry; D017785:Photons; D011829:Radiation Dosage; D011868:Radioisotopes / Q000737:chemistry; D011877:Radionuclide Imaging; D014965:X-Rays
chemical_list: D007457:Iodine Radioisotopes; D011868:Radioisotopes; D010165:Palladium; D006046:Gold