TY - JOUR
T1 - Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model
AU - Foged, Camilla
AU - Brodin, Birger
AU - Frøkjær, Sven
AU - Sundblad, Anne
N1 - Keywords: Chemistry, Physical; Dendritic Cells; Electrochemistry; Flow Cytometry; Fluorescent Dyes; Humans; Nanostructures; Nanotechnology; Particle Size; Polystyrenes; Surface Properties
PY - 2005
Y1 - 2005
N2 - Current vaccine development includes optimization of antigen delivery to antigen presenting cells, such as dendritic cells (DC). Particulate systems have attracted increasing attention in the development of vaccine delivery systems. In the present study, we investigated DC uptake of model fluorescent polystyrene particles with a broad size range and variable surface properties. Localization of particles was investigated using confocal laser scanning microscopy and uptake was quantified by flow cytometry. Immature DC were generated from mononuclear cells isolated from human blood. The polystyrene particles interacted with the DC throughout the tested diameter range of 0.04-15 microm in a time- and concentration-dependent manner. The optimal particle diameter for fast and efficient acquisition by a substantial percentage of the DC was 0.5 microm and below. The surface of 1 and 0.1 microm polystyrene particles was covalently modified with different polyaminoacids/proteins, yielding particles with varying surface charge. Uptake of 1 microm particles was greatly enhanced when particles displayed a positive surface charge. In general, the present findings establish that particle diameters of 0.5 microm and below were optimal for DC uptake; however uptake of larger particles could be greatly enhanced by rendering the particle surface positive. Whether increased particle uptake is correlated with increased immune responses, remains to be established.
AB - Current vaccine development includes optimization of antigen delivery to antigen presenting cells, such as dendritic cells (DC). Particulate systems have attracted increasing attention in the development of vaccine delivery systems. In the present study, we investigated DC uptake of model fluorescent polystyrene particles with a broad size range and variable surface properties. Localization of particles was investigated using confocal laser scanning microscopy and uptake was quantified by flow cytometry. Immature DC were generated from mononuclear cells isolated from human blood. The polystyrene particles interacted with the DC throughout the tested diameter range of 0.04-15 microm in a time- and concentration-dependent manner. The optimal particle diameter for fast and efficient acquisition by a substantial percentage of the DC was 0.5 microm and below. The surface of 1 and 0.1 microm polystyrene particles was covalently modified with different polyaminoacids/proteins, yielding particles with varying surface charge. Uptake of 1 microm particles was greatly enhanced when particles displayed a positive surface charge. In general, the present findings establish that particle diameters of 0.5 microm and below were optimal for DC uptake; however uptake of larger particles could be greatly enhanced by rendering the particle surface positive. Whether increased particle uptake is correlated with increased immune responses, remains to be established.
U2 - 10.1016/j.ijpharm.2005.03.035
DO - 10.1016/j.ijpharm.2005.03.035
M3 - Journal article
C2 - 15961266
SN - 0378-5173
VL - 298
SP - 315
EP - 322
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 2
ER -
