Abstract
Gold nanoparticles (AuNPs) are increasingly studied for cancer treatment purposes, as they can potentially improve both control and efficiency of the treatment. Intensive research is conducted in vitro on rodent and human cell lines to objectify the gain of combining AuNPs with cancer treatment and to understand their mechanisms of action. However, using nanoparticles in such studies requires thorough knowledge of their cellular uptake. In this study, we optimized single particle ICPMS (sp-ICPMS) analysis to qualify and quantify intracellular AuNP content after exposure of in vitro human breast cancer cell lines. To this aim, cells were treated with an alkaline digestion method with 5% TMAH, allowing the detection of gold with a yield of 97% on average. Results showed that under our experimental conditions, the AuNP size distribution appeared to be unchanged after internalization and that the uptake of particles depended on the cell line and on the exposure duration. Finally, the comparison of the particle numbers per cell with the estimates based on the gold masses showed excellent agreement, confirming the validity of the sp-ICPMS particle measurements in such complex samples.
Highlights
In 2016, 51 FDA-approved nanomedicines were available and 77 nanoproducts were on clinical trials, among which a large number were related to oncology [1]
Both ICPMS and sp-ICPMS measurements were performed on a Thermo iCAPQ quadrupole
Measurements by sp-ICPMS with time scans between 1 ms and 10 ms are based on the hypothesis that only one nanoparticle is detected during each scan
Summary
In 2016, 51 FDA-approved nanomedicines were available and 77 nanoproducts were on clinical trials, among which a large number were related to oncology [1]. Two major barriers to break down in nanomedicine are the uptake of nanoparticles by normal tissues and the nanoparticles’ inability to efficiently penetrate solid tumors. Overcoming these hurdles is of great interest during the development of efficient gold nanoparticles for therapy, since mass and number of internalized AuNPs and their aggregation state could be overriding parameters for cellular responses. Different pathways of internalization could drive to huge variation in intracellular accumulation of AuNPs and lead to different aggregation states or to sequestration in cellular compartments, and to different biological activities Studying these issues requires robust methods to characterize and quantify gold nanoparticle uptake into cells
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