TY - JOUR
T1 - Actively targeted gold nanoparticles as novel radiosensitizer agents
T2 - An in vivo head and neck cancer model
AU - Popovtzer, Aron
AU - Mizrachi, Aviram
AU - Motiei, Menachem
AU - Bragilovski, Dimitri
AU - Lubimov, Leon
AU - Levi, Mattan
AU - Hilly, Ohad
AU - Ben-Aharon, Irit
AU - Popovtzer, Rachela
N1 - Publisher Copyright:
© 2016 The Royal Society of Chemistry.
PY - 2016/2/7
Y1 - 2016/2/7
N2 - A major problem in the treatment of head and neck cancer today is the resistance of tumors to traditional radiation therapy, which results in 40% local failure, despite aggressive treatment. The main objective of this study was to develop a technique which will overcome tumor radioresistance by increasing the radiation absorbed in the tumor using cetuximab targeted gold nanoparticles (GNPs), in clinically relevant energies and radiation dosage. In addition, we have investigated the biological mechanisms underlying tumor shrinkage and the in vivo toxicity of GNP. The results showed that targeted GNP enhanced the radiation effect and had a significant impact on tumor growth (P < 0.001). The mechanism of radiation enhancement was found to be related to earlier and greater apoptosis (TUNEL assay), angiogenesis inhibition (by CD34 level) and diminished repair mechanism (PCNA staining). Additionally, GNPs have been proven to be safe as no evidence of toxicity has been observed.
AB - A major problem in the treatment of head and neck cancer today is the resistance of tumors to traditional radiation therapy, which results in 40% local failure, despite aggressive treatment. The main objective of this study was to develop a technique which will overcome tumor radioresistance by increasing the radiation absorbed in the tumor using cetuximab targeted gold nanoparticles (GNPs), in clinically relevant energies and radiation dosage. In addition, we have investigated the biological mechanisms underlying tumor shrinkage and the in vivo toxicity of GNP. The results showed that targeted GNP enhanced the radiation effect and had a significant impact on tumor growth (P < 0.001). The mechanism of radiation enhancement was found to be related to earlier and greater apoptosis (TUNEL assay), angiogenesis inhibition (by CD34 level) and diminished repair mechanism (PCNA staining). Additionally, GNPs have been proven to be safe as no evidence of toxicity has been observed.
UR - http://www.scopus.com/inward/record.url?scp=84956856037&partnerID=8YFLogxK
U2 - 10.1039/c5nr07496g
DO - 10.1039/c5nr07496g
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C2 - 26757746
AN - SCOPUS:84956856037
SN - 2040-3364
VL - 8
SP - 2678
EP - 2685
JO - Nanoscale
JF - Nanoscale
IS - 5
ER -