Design of hybrid multimodal poly(lactic-co-glycolic acid) polymer nanoparticles for neutrophil labeling, imaging and tracking.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) incorporating quantum dots (QDs), superparamagnetic iron oxide nanoparticles (SPIONs) and gold (Au) NPs for neutrophil labeling were fabricated via the w/o/w double emulsion method. QDs and SPIONs were entrapped in the PLGA core during emulsification while Au NPs were assembled on top of the PLGA NPs via electrostatic interactions. Transmission Electron Microscopy, Scanning Electron Microscopy and Confocal Scanning Laser Microscopy (CLSM) were applied to characterize the hybrid PLGA NPs. The uptake of the hybrid PLGA NPs by human neutrophils was studied by Flow Cytometry and confocal microscopy. In addition, the induction of reactive oxygen species (ROS) in neutrophils after incubation with the hybrid PLGA NPs was assessed. Magnetophoresis experiments showed that neutrophils with internalized hybrid PLGA NPs can be effectively laterally displaced towards the magnetic field. Magnetic Resonance Imaging of the hybrid PLGA NPs resulted in images with a contrast enhancement linearly dependent on the concentration of the hybrid PLGA NPs. Research reported in this work is relevant for imaging, tracking and manipulating neutrophils and has potential for in vivo applications, e.g., tumor visualization and localized photothermal treatment.