Statistical analysis of nanoparticle dosing in a dynamic cellular system

Abstract

The delivery of nanoparticles into cells is important in therapeutic applications and in nanotoxicology. Nanoparticles are generally targeted to receptors on the surfaces of cells and internalized into endosomes by endocytosis, 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.

Reply to 'The interface of nanoparticles with proliferating mammalian cells'

“…The work of Panet et al 1 is a welcome addition to earlier reports on nanoparticle uptake in proliferating cells 2,3 , and provides us the opportunity to further reinforce and clarify the main points of our paper 2 on the coupling of cell cycle progression and nanoparticle accumulation.…”

Intracellular partitioning of cell organelles and extraneous nanoparticles during mitosis

“…The dilution of endocytosed QDs upon cell division leads to an asymmetric segregation of endosomes and thus of QDs [88]. Using a statistical model, the same group further showed that partitioning of nanoparticles upon cell division is a random and asymmetric event [89].…”

“…Gold particles < 10 nm: through NPCs [88,89] 10-20 nm: nuclear enclosure > 20 nm: nuclear exclusion Quantum dots Symmetric or asymmetric segregation within endosomes; nuclear exclusion [79,80] Iron oxide nanoparticles [87] Nonviral gene delivery particles Lipid carriers unknown [5,8,[13][14][15][16][17] Polymer carriers [5,8,12] …”

Quantifying Nanoparticle–Cell Interactions

“…Quantitative cell (optical) imaging has been used to show that the nanoparticle uptake into cellular vesicles proceeds by a random process [3]. This was achieved by assuming groups of quantum dots within vesicles act as discrete and stable fluorescent sources.…”

“…Quantitative analysis of the serum-quantum dot solution used in [3] and [4] shows a heterogeneous dispersion of dots with a high frequency of monodisperse dots plus a significant (volume) fraction of agglomerates. Quantitative TEM imaging of cellular uptake shows a similar distribution of uptake in vesicles and we have correlated this distribution to the distribution identified by optical metrology [3].…”