Total reflection X-ray fluorescence based quantification of gold nanoparticles in cancer cells

In the last two decades, nanoparticles of different shapes, sizes and materials have been investigated for various nanomedicine applications, ranging from imaging to radiation therapy, in efforts to improve conventional cancer therapies. The current focus of nanomedicine is to increase the delivery and cellular uptake of nanoparticles. Thus, further development and advancement of the field requires accurate means to quantitatively assess nanoparticle concentration in cells. Inductively Coupled Plasma (ICP) based methods are currently being used for nanoparticle quantification. Such methods however require extensive sample preparation and large sample volumes, which poses a challenge when dealing with small sample volumes with low concentration. This work describes the development and validation of a total reflection X-ray fluorescence (TXRF) based quantification method for trace-level gold nanoparticles in an organic matrix. Suitable internal standards, fitting approaches and sample preparation methods that yield acceptable recovery rates were investigated. The developed method was validated with reference material nanoparticles. Recovery rates of (102.7 ± 3.7)% and (100.9 ± 5.1)% were achieved for nanoparticles in an ionic solution and organic matrix respectively. These results suggest that TXRF is an adequate technique to accurately quantify gold nanoparticle uptake in cancer cells.