Actively targeted gold nanoparticles as novel radiosensitizer agents: an in vivo head and neck cancer model

被引:84
作者
Popovtzer, Aron [1 ,4 ]
Mizrachi, Aviram [1 ,4 ]
Motiei, Menachem [2 ,3 ]
Bragilovski, Dimitri [1 ]
Lubimov, Leon [1 ]
Levi, Mattan [4 ]
Hilly, Ohad [1 ]
Ben-Aharon, Irit [1 ,4 ]
Popovtzer, Rachela [2 ,3 ]
机构
[1] Rabin Med Ctr, Davidoff Canc Ctr, Inst Oncol, Head & Neck Canc Radiat Clin, IL-49100 Petah Tiqwa, Israel
[2] Bar Ilan Univ, Fac Engn, IL-5290002 Ramat Gan, Israel
[3] Bar Ilan Univ, Inst Nanotechnol & Adv Mat, IL-5290002 Ramat Gan, Israel
[4] Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel
关键词
SQUAMOUS-CELL CARCINOMA; RADIATION; RADIOTHERAPY; ENHANCEMENT;
D O I
10.1039/c5nr07496g
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:2678 / 2685
页数:8
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