Unraveling the uptake mechanisms of mannan nanogel in bone-marrow-derived macrophages

The mechanisms associated with the cellular internalization of nanomedicines must be carefully considered when designing drug- and vaccine-delivery systems. The cellular fate and effects of nanomedicines depend to a large extent on the cell uptake routes. A self-assembled mannan nanogel is developed as a vaccination platform for antigen and adjuvant delivery. The mannan nanogel uptake by murine bone-marrow-derived macrophages is found to be time-, concentration-, and energy-dependent, involving mannose-receptor-mediated phagocytosis and clathrin-mediated endocytosis. The nanogel is also visualized in the cytosol suggesting endolysosomal escape. These results indicate that mannan nanogel is a promising versatile carrier for intracellular delivery of vaccines or therapeutic agents.S. A. F. is the recipient of a fellowship from International Iberian Nanotechnology Laboratory (INL). The authors wish to acknowledge the financial support from the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal), trough PTDC. M. V., P.o M. and A. C. were supported by SUDOE-FEDER (IMMUNONET, SOE1/P1/E014). The technical support on confocal studies by Lucilia Goreti Ribeiro Pinto from Life and Health Sciences Research Institute (ICVS), School of Health Sciences, Braga, Portugal, is gratefully acknowledged. The authors thankfully acknowledge the important scientific comments, helpful advice and critical review given by Prof. Dr. Arwyn Tomos Jones, Welsh School of Pharmacy, Cardiff University, Cardiff