Statistical analysis of nanoparticle dosing in a dynamic cellular system.
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.
Centre for Nanohealth, College of Engineering, Swansea University, Swansea, SA2 8PP, UK. h.d.summers@swansea.ac.uk
Huw D
HD
Summers
Paul
P
Rees
Mark D
MD
Holton
M Rowan
MR
Brown
Sally C
SC
Chappell
Paul J
PJ
Smith
Rachel J
RJ
Errington
D000327:Adsorption; D000465:Algorithms; D016010:Binomial Distribution; D002460:Cell Line; D002477:Cells / Q000737:chemistry* / Q000166:cytology*; D003627:Data Interpretation, Statistical; D004058:Diffusion; D004705:Endocytosis; D011992:Endosomes; D006801:Humans; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D016012:Poisson Distribution; D045663:Quantum Dots; D013050:Spectrometry, Fluorescence
Proc Natl Acad Sci U S A. 1979 Jul;76(7):3330-7
226968
Biometrics. 1949 Jun;5(2):162-4
18151958
Cell Cycle. 2010 Jan 1;9(1):121-30
20016285
Angew Chem Int Ed Engl. 2007;46(28):5397-401
17357103
Nat Rev Drug Discov. 2010 Jan;9(1):29-42
20043027
Nanomedicine. 2005 Sep;1(3):193-212
17292079
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11613-8
18697944
Eur J Cell Biol. 2002 Mar;81(3):117-24
11998863
Toxicol In Vitro. 2010 Apr;24(3):1009-18
20006982
Nat Rev Clin Oncol. 2010 May;7(5):266-76
20351700
Nano Lett. 2006 Sep;6(9):2049-59
16968024
J Am Chem Soc. 2007 Jul 11;129(27):8438-9
17569542
Trends Cell Biol. 2009 Jan;19(1):1-7
19091567
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20576-81
18077369
Biochim Biophys Acta. 2001 Dec 5;1568(2):147-54
11750762
Curr Biol. 2001 May 1;11(9):644-51
11369227
J Vet Sci. 2006 Dec;7(4):321-6
17106221
Toxicol Sci. 2007 Feb;95(2):300-12
17098817
Nat Biotechnol. 2003 Jan;21(1):47-51
12459736
Int J Pharm. 2008 Apr 16;354(1-2):34-8
18068916
Cell. 2004 Sep 3;118(5):591-605
15339664
Nat Rev Cancer. 2005 Mar;5(3):161-71
15738981
Biophys J. 2008 May 15;94(10):3790-7
18234813
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12617-21
12235356
Nature. 2003 Mar 6;422(6927):37-44
12621426
Cell. 2008 Nov 28;135(5):801-12
19041746
PLoS Biol. 2006 Dec;4(12):e417
17147470
Nano Lett. 2006 Apr;6(4):662-8
16608261
J Am Chem Soc. 2004 Jun 2;126(21):6520-1
15161257