NDLI: Dynamics of bionanoparticle targeting in mixtures of human tumour cells by validated population balance modelling

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Soft Matter Vol - 6 Issue - 5

Soft Matter Vol - 6 Issue - 4

Soft Matter Vol - 6 Issue - 3

Dynamics of bionanoparticle targeting in mixtures of human tumour cells by validated population balance modelling

Content Provider	Royal Society of Chemistry (RSC)
Author	Sundmacher, Kai Rollié, Sascha Lendeckel, Uwe Naumann, Michael Reichl, Udo
Copyright Year	2010
Abstract	Preferential aggregation of bionanoparticles to different human suspension cell lines preceding cellular uptake by endocytosis was investigated by a 3-dimensional discrete population balance model. Property space was reduced by excluding intercellular aggregation in accordance with experimental evidence and by establishing an adaptive grid with full property resolution in areas of high particle or cell densities. The aggregation rates are based on deterministic models from colloidal sciences, adapted to include biologically specific aggregation in addition to unspecific aggregation. While the collision frequency is described by the Smoluchowski kernel for Brownian motion, the collision efficiency is modelled by a kernel considering inhomogeneous surface patches. The patch encounter probability and the interaction potential energies embedded in the stability ratio gain dominant influence on the aggregation kinetics. Given a cell specific receptor density as input parameter, the preferential aggregation of bionanoparticles to U-937 cells in mixture with KARPAS-299 cells was successfully simulated. Fast specific biological aggregation is superimposed on slow unspecific aggregation. The distribution of adsorbed bionanoparticles per cell initially broadens considerably until all receptors are saturated, then narrows down to a quasi-equilibrium state where only unspecific aggregation persists. A low probability of bionanoparticle-receptor encounters, based on considerations concerning cell and receptor geometries, causes a rate limitation of biologically specific aggregation despite the high bionanoparticle to cell concentration ratio and purely attractive interaction potentials. Validation experiments with IgG1, CD13 and CD33 antibodies were performed by flow cytometry. By appropriate gating separate aggregation dynamics could be gained for each cell type. Since the expression levels of antigens on the cell surfaces vary between the experiments and because the quantification of adsorbed antibody numbers remains difficult, dimensionless experimental data is compared to the simulations with very good agreement. Selective and specific drug delivery to target cells might represent a future application of this principle.
Starting Page	1203
Ending Page	1216
Page Count	14
File Format	HTM / HTML PDF
ISSN	1744683X
Volume Number	6
Issue Number	6
Journal	Soft Matter
DOI	10.1039/b919122d
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Brownian motion Flow cytometry Endocytosis Marian Smoluchowski Integral transform Cell surface receptor Antibody Smoluchowski Drug delivery Alanine aminopeptidase CD33
Content Type	Text
Resource Type	Article
Subject	Chemistry Condensed Matter Physics

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