Cell-to-cell heterogeneous association of prostate cancer with gold nanoparticles elucidated by single-cell inductively coupled plasma mass spectrometry

Understanding the uptake and biodistribution of nanoparticles (NPs) into the cells is essential to evaluate the mechanism of action, efficacy, and safety of nanosystems applied in clinical diagnostics or as drug carriers. The estimation of NPs per cell is typically performed by sampling a known number of cells and measuring the average concentration of NPs. However, this approach is limited and does not provide information on the NP distribution's heterogeneity. Thus, a novel method to quantify the uptake of AuNPs (either internalized or firmly bound to the cell membrane) in individual prostate cancer cells (PC-3) was developed. The method is based on Single Cell Inductively Coupled Plasma Mass Spectrometry (SC-ICP-MS) and allows the accurate quantification of gold concentrations at the attogram (ag) per cell level. The procedure was successfully applied to understand the interaction of AuNPs with PC-3 cells, showing cell-to-cell variances in the ability to uptake AuNPs. By varying the AuNPs concentration from 2 to 32 mu g L-1 increased the population of PC-3 cells containing AuNPs from 1.83 to 38.36 %, respectively. At the higher exposure concentration, 22.79, 12.83, and 1.79 % of the cells presented 1, 2, and 3 AuNPs/cell, respectively. Moreover, a dose-dependent increase in the number of cells containing AuNPs/ cell over the exposure period was observed, although only a tiny fraction (2.2 and 3.8 %) was taken up by cells. The present paper opens new perspectives for further investigations toward understanding NPs-cell interactions, leading to better design of nano-based drug delivery approaches.

Automated summary

This study developed a new method to quantify the uptake of gold nanoparticles in individual cancer cells and revealed differences in the uptake ability among cells.