Highlights from the latest articles in nanoparticle cellular interactions.

Abstract

2014 Reversibly programmed peripheral blood mononuclear cells recognize & suppress cancer cells Evaluation of: Gabrielse K, Gangar A, Kumar N et al. Reversible re-programing of cell–cell interactions. Angew. Chem. Int. Ed. Engl. 53(20), 5112–5116 (2014). Over the past few decades, much attention has been given to cell surface modification approaches allowing the control of cell– cell interactions. Chemical crosslinking to membrane proteins, intercalation of lipidconjugated proteins into cell membranes or genetic modifications of the cells have demonstrated some efficiency, but limitations include a short lifetime and nonreversibility. Here, Gabrielse et al. used lipid-chemically self-assembled nanorings (lipid-CSANs) that intercalated rapidly into plasma membranes, and labeled them with fluorophores, drugs, proteins or oligonucleotides. Confocal microscopy and flow cytometry experiments demonstrated a uniform labeling of cell membranes, with little or no loss of signal over the first 24 h. Nanorings were formed by self-assembly of phospholipidconjugated methotrexate (MTX) dimers (bis-MTX) with a recombinant fusion protein of a DHFR dimer (DHFR2) fused to single-chain anti bodies (scFvs) or peptides conjugated to fluoro phores. Lipid-CSANs were fused with antibodies targeting the cancerspecific antigen EpCAM to bind specifically to the EpCAM-positive breast cancer cell line MCF-7. Peripheral blood mononuclear cells treated with anti-EpCAM-lipid-CSANs did bind specifically to MCF-7 cells but also induced a significant cell lysis, as demonstrated by the LDH release assay and timelapsed video microscopy. Therefore, the antiEpCAM lipid nanorings were able to redirect peripheral blood mononuclear cells towards cancer cells, but also caused selective target antigen-directed cell lysis. Notably, this specific nanostructure can be disassembled easily by adding the nontoxic, US FDA-approved, DHFR inhibitor trimethoprim, which allows temporal control of the effects of the lipidCSANs and explains the so-called reversible reprogramming of cell–cell interactions induced by lipid-CSANs proposed by Gabrielse and colleagues.