Click hybridization of immune cells and polyamidoamine dendrimers

Abstract

Immobilizing highly branched polyamidoamine (PAMAM) dendrimers to the cell surface represents an innovative method of enhancing cell surface loading capacity to deliver therapeutic and imaging agents. In this work, hybridized immune cells, that is, macrophage RAW264.7 (RAW), with PAMAM dendrimer G4.0 (DEN) on the basis of bioorthogonal chemistry are clicked. Efficient and selective cell surface immobilization of dendrimers is confirmed by confocal microscopy. Viability and motility of RAW-DEN hybrids remain the same as untreated RAW cells according to WST-1 assay and wound closure assay. Furthermore, Western blot analysis reveals that there are no significant alterations in the expression levels of signaling molecules AKT, p38, and NFκB (p65) and their corresponding activated (phosphorylated) forms in RAW cells treated with azido sugar and dendrimer, indicating that the hybridization process neither induced cell stress response nor altered normal signaling pathways. Taken together, this work shows the feasibility of applying bioorthogonal chemistry to create cell-nanoparticle hybrids and demonstrates the noninvasiveness of this cell surface engineering approach.

Keywords: bioorthogonal chemistry; cell surface engineering; dendrimers; drug delivery; imaging.