Statistical analysis of nanoparticle dosing in a dynamic cellular system

The delivery of nanoparticles into cells is important in therapeutic applications(1-3) and in nanotoxicology(4). Nanoparticles are generally targeted to receptors on the surfaces of cells and internalized into endosomes by endocytosis(5-9), but the kinetics of the process and the way in which cell division redistributes the particles remain unclear. Here we show that the chance of success or failure of nanoparticle uptake and inheritance is random. Statistical analysis of nanoparticle-loaded endosomes indicates that particle capture is described by an over-dispersed Poisson probability distribution that is consistent with heterogeneous adsorption and internalization. Partitioning of nanoparticles in cell division is random and asymmetric, following a binomial distribution with mean probability of 0.52-0.72. These results show that cellular targeting of nanoparticles is inherently imprecise due to the randomness of nature at the molecular scale, and the statistical framework offers a way to predict nanoparticle dosage for therapy and for the study of nanotoxins.