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• W2035798790 abstract "Purpose/Objective(s)To investigate the correlation between increased density of ionizations (DI) and the enhanced biological effect caused by gold nanoparticles (AuNP) internalized within cells.Materials/MethodsCellular internalization of AuNP was evaluated in prostate cancer (PC) cells quantitatively by inductively coupled plasma-mass spectrometry (ICP-MS) and qualitatively by transmission electron microscopy (TEM) for PEGylated AuNP (pAuNP) and for conjugated AuNP to goserelin (gAuNP), a decapeptide analog of luteinizing hormone releasing hormone. Cellular uptake peaked after 24 h of incubation with 0.1% w/w of gold. Clonogenic survival was assessed at this time point for Ir-192, Cs-137 and 6MV beams using customized and dosimetrically validated radiation setups. PENELOPE Monte Carlo code was used to simulate ionization events under these treatment conditions. The simulation geometry matched the intracellular gold content detected with ICP-MS and assumed 50 nm spherical AuNP randomly distributed outside a 5.0 μm diameter nuclear region within the cytoplasm of a 12.5 μm diameter tissue-equivalent cell. The energy spectrum and yield of secondary photoelectrons and Auger electrons were recorded. Electrons and photons were transported up to 1eV and maximum angular deflections of 0.05 were allowed.ResultsThe absolute intracellular concentration of gAuNP (0.01% w/w) was found to be 5-fold higher than pAuNP. The relative geographical distribution on TEM imaging showed clustering of gAuNP in endosomes whereas pAuNP were singly dispersed in the cytoplasm. Monte Carlo modeling predicted an enhancement in DI in the cytoplasm of 62%, 50% and 15% for the Ir-192, Cs-137 and 6MV beams, respectively for gAuNP compared to 33%, 29% and 5%, respectively for pAuNP. The effective fluence of electrons in the cytoplasm was highly dependent on the amount and location of gold within the cell. Radiosensitization enhancement factors (REFs) calculated at the 10% surviving fraction of clonogenic survival curves were 1.45, 1.23 and 1.21 for the Ir-192, Cs-137 and 6MV beams, respectively for gAuNP compared to 1.16, 1.09 and 1.07, respectively for pAuNR.ConclusionsGoserelin conjugation effectively targets AuNP to PC cells, and the resulting internalization leads to energy modulation of the incident radiation beam. The increased yield of secondary electrons is proportional to the concentration of gold within cells, locally enhancing the DI in the cytoplasm and correlating with REFs on clonogenic assays. Purpose/Objective(s)To investigate the correlation between increased density of ionizations (DI) and the enhanced biological effect caused by gold nanoparticles (AuNP) internalized within cells. To investigate the correlation between increased density of ionizations (DI) and the enhanced biological effect caused by gold nanoparticles (AuNP) internalized within cells. Materials/MethodsCellular internalization of AuNP was evaluated in prostate cancer (PC) cells quantitatively by inductively coupled plasma-mass spectrometry (ICP-MS) and qualitatively by transmission electron microscopy (TEM) for PEGylated AuNP (pAuNP) and for conjugated AuNP to goserelin (gAuNP), a decapeptide analog of luteinizing hormone releasing hormone. Cellular uptake peaked after 24 h of incubation with 0.1% w/w of gold. Clonogenic survival was assessed at this time point for Ir-192, Cs-137 and 6MV beams using customized and dosimetrically validated radiation setups. PENELOPE Monte Carlo code was used to simulate ionization events under these treatment conditions. The simulation geometry matched the intracellular gold content detected with ICP-MS and assumed 50 nm spherical AuNP randomly distributed outside a 5.0 μm diameter nuclear region within the cytoplasm of a 12.5 μm diameter tissue-equivalent cell. The energy spectrum and yield of secondary photoelectrons and Auger electrons were recorded. Electrons and photons were transported up to 1eV and maximum angular deflections of 0.05 were allowed. Cellular internalization of AuNP was evaluated in prostate cancer (PC) cells quantitatively by inductively coupled plasma-mass spectrometry (ICP-MS) and qualitatively by transmission electron microscopy (TEM) for PEGylated AuNP (pAuNP) and for conjugated AuNP to goserelin (gAuNP), a decapeptide analog of luteinizing hormone releasing hormone. Cellular uptake peaked after 24 h of incubation with 0.1% w/w of gold. Clonogenic survival was assessed at this time point for Ir-192, Cs-137 and 6MV beams using customized and dosimetrically validated radiation setups. PENELOPE Monte Carlo code was used to simulate ionization events under these treatment conditions. The simulation geometry matched the intracellular gold content detected with ICP-MS and assumed 50 nm spherical AuNP randomly distributed outside a 5.0 μm diameter nuclear region within the cytoplasm of a 12.5 μm diameter tissue-equivalent cell. The energy spectrum and yield of secondary photoelectrons and Auger electrons were recorded. Electrons and photons were transported up to 1eV and maximum angular deflections of 0.05 were allowed. ResultsThe absolute intracellular concentration of gAuNP (0.01% w/w) was found to be 5-fold higher than pAuNP. The relative geographical distribution on TEM imaging showed clustering of gAuNP in endosomes whereas pAuNP were singly dispersed in the cytoplasm. Monte Carlo modeling predicted an enhancement in DI in the cytoplasm of 62%, 50% and 15% for the Ir-192, Cs-137 and 6MV beams, respectively for gAuNP compared to 33%, 29% and 5%, respectively for pAuNP. The effective fluence of electrons in the cytoplasm was highly dependent on the amount and location of gold within the cell. Radiosensitization enhancement factors (REFs) calculated at the 10% surviving fraction of clonogenic survival curves were 1.45, 1.23 and 1.21 for the Ir-192, Cs-137 and 6MV beams, respectively for gAuNP compared to 1.16, 1.09 and 1.07, respectively for pAuNR. The absolute intracellular concentration of gAuNP (0.01% w/w) was found to be 5-fold higher than pAuNP. The relative geographical distribution on TEM imaging showed clustering of gAuNP in endosomes whereas pAuNP were singly dispersed in the cytoplasm. Monte Carlo modeling predicted an enhancement in DI in the cytoplasm of 62%, 50% and 15% for the Ir-192, Cs-137 and 6MV beams, respectively for gAuNP compared to 33%, 29% and 5%, respectively for pAuNP. The effective fluence of electrons in the cytoplasm was highly dependent on the amount and location of gold within the cell. Radiosensitization enhancement factors (REFs) calculated at the 10% surviving fraction of clonogenic survival curves were 1.45, 1.23 and 1.21 for the Ir-192, Cs-137 and 6MV beams, respectively for gAuNP compared to 1.16, 1.09 and 1.07, respectively for pAuNR. ConclusionsGoserelin conjugation effectively targets AuNP to PC cells, and the resulting internalization leads to energy modulation of the incident radiation beam. The increased yield of secondary electrons is proportional to the concentration of gold within cells, locally enhancing the DI in the cytoplasm and correlating with REFs on clonogenic assays. Goserelin conjugation effectively targets AuNP to PC cells, and the resulting internalization leads to energy modulation of the incident radiation beam. The increased yield of secondary electrons is proportional to the concentration of gold within cells, locally enhancing the DI in the cytoplasm and correlating with REFs on clonogenic assays." @default.
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• W2035798790 date "2013-10-01" @default.
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• W2035798790 title "Enhanced Radiosensitization by Tumor-Targeting Gold Nanoparticles: A Paradigm for Energy Modulated Radiation Therapy (EMRT)" @default.
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• W2035798790 doi "https://doi.org/10.1016/j.ijrobp.2013.06.1743" @default.
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