Multimodal imaging of nanovaccine carriers targeted to human dendritic cells

L. J. CRUZ; P. TACKEN; F. BONETTO; S. BUSCHOW; H. CROES; M. WIJERS; J. DE VRIES; C. G. FIGDOR

MOLECULAR PHARMACEUTICS

AMER CHEMICAL SOC

Año: 2011 vol. 8 p. 520 - 531

1543-8384

Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy against cancer and infectious diseases. The targeted delivery of nanovaccine particles (NPs) to DCs in vivo is a promising strategy to enhance immuneresponses. Here, targeted nanovaccine carriers were generated that allow multimodal imaging of nanocarrier
DC interactions from the subcellular to the organism level. These carriers weremade of biodegradable poly(D,L-lactide-co-glycolide) harboring superparamagnetic iron oxide particles (SPIO) and fluorescently labeled antigen in a single particle. Targeted delivery wasfacilitated by coating the NPs with antibodies recognizing the DC-specific receptor DC-SIGN. The fluorescent label allowed for rapid analysis and quantification of specific versus nonspecific uptake of targeted NPs by DCs compared to other blood cells. In addition, it showed that part of the encapsulated antigen reached the lysosomal compartment of DCs within 24 h. Moreover, thepresence of fluorescent label did not prevent the antigen from being presented to antigen-specific T cells. The incorporated SPIO was applied to track the NPs at subcellular cell organel level using transmission electron microscopy (TEM). NPs were found within endolysosomal compartments, where part of the SPIO was already released within 24 h. Furthermore, part of the NPs seemed tolocalize within the cytoplasm. Ex vivo loading of DCs with NPs resulted in efficient labeling and  detection by MRI and did not abolish cell migration within collagen scaffolds. In conclusion,  incorporation of two imaging agents within a single carrier allows tracking of targeted nanovaccines on a subcellular, cellular and possibly organism level, thereby facilitating rational design of in vivo targeted vaccination strategies.