Cytokinfunctionalized NANOCYTES® for cancer therapy

At Fraunhofer IGB, biological-synthetic hybrid particles were developed which simulate the conditions on cell surfaces. On the surface of these cell-mimetic nanoparticles - which mimic cells - membrane proteins are bound so that their biological properties are fully preserved. Such NANOCYTES® are interesting tools for both basic research and clinical development.

The Cytokine TNF

The cytokine tumor necrosis factor α (TNF-α) occurs in nature both in dissolved form and as a component of the outer membrane of cells. The dissolved form of the cytokine has a different effect than the bound form. Dissolved TNF-α can only activate one of two TNF receptors and hence only transmit a specific signal to the cell, whereas membrane-bound TNF can activate two different receptors. For a long time, only the solute molecule was available to researchers for their experiments, which meant that only one signalling pathway could be investigated.

Cell experiment with TNF-NANOCYTES

TNF Nanocytes Apoptose L.
NANOCYTES® (red particles) functionalised with TNF bind to receptors in cells (green) and thus trigger cell death within minutes in cell experiments.

Together with researchers from the University of Stuttgart (Prof. Pfizenmaier and Prof. Scheurich), TNF-α was attached to nano- and microparticles developed at Fraunhofer IGB. These so-called cell-mimetic core-shell particles act like cells that carry the cytokine TNF on their outer shell.

In cell experiments, the TNF-NANOCYTES® unfold their full effectiveness, which otherwise only the membrane-bound cytokine has. This was shown in specially prepared cells which react to an activation of the TNF-receptor-2 with programmed cell death (apoptosis) and thus make the activation detectable (Figure): After TNF-NANOCYTES® have docked to TNF-receptor-2 in the cell membrane, the apoptosis program is started in the cells.

The TNF-NANOCYTES® can now be used to investigate both TNF-α-mediated signalling pathways. At the same time, the example of TNF-NANOCYTES® shows that NANOCYTES® can improve the efficacy of biopharmaceuticals by allowing a formulation inspired by nature.