Original Article
Preferential uptake of chitosan-coated PLGA nanoparticles by primary human antigen presenting cells

https://doi.org/10.1016/j.nano.2019.102073Get rights and content
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Abstract

Biodegradable polymeric nanoparticles (NP) made from poly (lactid-co-glycolide) acid (PLGA) and chitosan (CS) hold promise as innovative formulations for targeted delivery. Since interactions of such NP with primary human immune cells have not been characterized, yet, here we assessed the effect of PLGA or CS-PLGA NP treatment on human peripheral blood mononuclear cells (PBMC), as well as on monocyte-derived DC (moDC). Amongst PBMC, antigen presenting cells (APC) showed higher uptake of both NP preparations than lymphocytes. Furthermore, moDC internalized CS-PLGA NP more efficiently than PLGA NP, presumably because of receptor-mediated endocytosis. Consequently, CS-PLGA NP were delivered mostly to endosomal compartments, whereas PLGA NP primarily ended up in lysosomes. Thus, CS-PLGA NP confer enhanced delivery to endosomal compartments of APC, offering new therapeutic options to either induce or modulate APC function and to inhibit pathogens that preferentially infect APC.

Graphical Abstract

PLGA and chitosan-coated PLGA nanoparticles (NP) were synthesized and their interaction with human primary immune cells was evaluated. Within PBMC, antigen presenting cells (APC), including monocytes and DC, took up both NP preferentially. Further analysis in monocyte-derived dendritic cells (moDC), a commonly used model for APC, revealed that chitosan-coated PLGA NP were preferentially delivered to endosomal compartments. Additionally, both NP preparations showed low cytotoxic effects and no immunostimulatory effects. Thus, these results demonstrate that CS-PLGA NP are a promising vehicle to target discrete endosomal compartments within APC.

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Key words

Nanoparticles
PLGA NP
Chitosan-PLGA NP
PBMC
Monocyte-derived DC
Intracellular trafficking

Cited by (0)

Funding: This study was partially supported by the Helmholtz “Zukunftsthema Immunology und Inflammation” [ZT-0027] and by the Deutsche Forschungsgemeinschaft (DFG, Joint French-German Project cGAS-VAV [406922110]) to U.K.

Acknowledgments: The authors would like to thank Dr. Chiara De Rossi for support in performing TEM visualization studies. We thank Dr. Chintan Chhatbar for scientific discussion.

Conflict of interest: The authors declare no conflict of interest

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© 2019 The Author(s). Published by Elsevier Inc.