A method for the efficient cellular uptake and retention of small modified gold nanoparticles for the radiosensitization of cells

被引:28
作者
Burger, Nina [1 ]
Biswas, Abin [1 ,2 ]
Barzan, Daniel [3 ,4 ]
Kirchner, Anne [1 ]
Hosser, Hiltraud [5 ]
Hausmann, Michael [2 ]
Hildenbrand, Georg [1 ,2 ]
Herskind, Carsten [1 ]
Wenz, Frederik [1 ]
Veldwijk, Marlon R. [1 ]
机构
[1] Heidelberg Univ, Univ Med Mannheim, Med Fac Mannheim, Dept Radiat Oncol, D-68135 Mannheim, Germany
[2] Heidelberg Univ, Kirchhoff Inst Phys, Heidelberg, Germany
[3] Heidelberg Univ, Cellnetworks Cluster, Heidelberg, Germany
[4] Heidelberg Univ, Inst Phys Chem, Heidelberg, Germany
[5] Heidelberg Univ, Univ Med Mannheim, Med Fac Mannheim, Ctr Biomed & Med Technol Mannheim CBTM,Dept Anat, D-68135 Mannheim, Germany
关键词
Gold nanoparticles; Auger electrons; Transfection; Radiosensitization; Uptake; Size dependency; DOSE ENHANCEMENT; X-RAYS; TOTAL-BODY; TUMOR; ACCUMULATION; IRRADIATION; MECHANISM; DAMAGE; SIZE;
D O I
10.1016/j.nano.2014.03.011
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Gold nanoparticles (GNP) enhance the absorbance of photons thereby increasing emission of Auger-/photoelectrons in the nm-mu m range. Yet, a major disadvantage is their diameter-dependent cellular uptake with an optimum of similar to 50 nm which may not offer optimal radiosensitization. A method was developed to enhance the uptake of small GNP. GNP (10 nm) were linked to DNA and transferred into HeLa cells by transient transfection (GNP-DT). Treatment of cells with GNP-DT resulted in a strong perinuclear focal accumulation, whereas this was dimmer and sparser for GNP-T (lacking DNA) and close to background levels in GNP-treated cells. Only GNP-DT showed a significant radiosensitizing effect (p = 0.005) on clonogenic survival using clinically relevant megavolt x-rays. Our novel method markedly increases the uptake/retention and alters the localization of small GNP in cells compared to unmodified GNP. This work finally enables studying the radiosensitizing effects of differentially sized GNP.
引用
收藏
页码:1365 / 1373
页数:9
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